Jpog April 2013 Id

JAN/FEB 2012 Mar/Apr 2013 Vol. Vol. 38 39 No. No.
12
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
Your partner in paediatric and O&G practice
ISSN 1016-0124 (INDONESIA)
CME ARTICLE
P 3 SK
Imaging in Ectopic PregnancyRevisited

JOURNAL WATCH
OBSTETRICS
Hypertension in Pregnancy
PAEDIATRICS
Evaluation of the Acute Abdomen

Gynaecology
The Management of Perimenopausal Menstrual Symptoms

www.jpog.com
Get your copy of JPOG today and earn SKP IDI
M AR / APR Vol. 39
2013 No. 2
Journal Watch
45 HRT and cardiovascular risk in early menopause Maternal obesity and neonatal death in Africa Comparing drugs for tocolytic therapy 46 Single progesterone level to detect non-viability of early pregnancy Equity in maternal and child health interventions Changes in money given for maternal, newborn, and child health in Countdown countries
45
47 MDG 4 success of Niger Clinicians gut feeling about serious infection in children BMI and cardiovascular risk factors in children
48 Physical activity interventions in children High-sugar drinks and body weight in children and adolescents Classroom-based CBT for adolescents at risk of depression: Not effective
47
Editorial Board
Board Director, Paediatrics Professor Pik-To Cheung Associate Professor Department of Paediatrics and Adolescent Medicine The University of Hong Kong Board Director, Obstetrics and Gynaecology Professor Pak-Chung Ho Head, Department of Obstetrics and Gynaecology The University of Hong Kong
Professor Biran Affandi University of Indonesia Dr Karen Kar-Loen Chan The University of Hong Kong Associate Professor Oh Moh Chay KK Womens and Childrens Hospital, Singapore Associate Professor Anette Jacobsen KK Womens and Childrens Hospital, Singapore Professor Rahman Jamal Universiti Kebangsaan Malaysia Dato Dr Ravindran Jegasothy Hospital Kuala Lumpur, Malaysia Associate Professor Kenneth Kwek KK Womens and Childrens Hospital, Singapore Dr Siu-Keung Lam Kwong Wah Hospital, Hong Kong Professor Terence Lao Chinese University of Hong Kong Dr Kwok-Yin Leung The University of Hong Kong
Dr Tak-Yeung Leung Chinese University of Hong Kong Professor Tzou-Yien Lin Chang Gung University, Taiwan Professor Somsak Lolekha Ramathibodi Hospital, Thailand Professor Lucy Chai-See Lum University of Malaya, Malaysia Professor SC Ng National University of Singapore Professor Hextan Yuen-Sheung Ngan The University of Hong Kong Professor Carmencita D Padilla University of the Philippines Manila Professor Seng-Hock Quak National University of Singapore Dr Tatang Kustiman Samsi University of Tarumanagara, Indonesia Professor Perla D Santos Ocampo University of the Philippines Associate Professor Alex Sia KK Womens and Childrens Hospital, Singapore
Dr Raman Subramaniam Fetal Medicine and Gynaecology Centre, Malaysia Professor Walfrido W Sumpaico MCU-DFT Medical Foundation, Philippines Professor Cheng Lim Tan KK Womens and Childrens Hospital, Singapore Associate Professor Kok Hian Tan KK Womens and Childrens Hospital, Singapore Dr Surasak Taneepanichskul Chulalongkorn University, Thailand Professor Eng-Hseon Tay Thomson Womens Cancer Centre, Singapore Professor PC Wong National University of Singapore Dr George SH Yeo KK Womens and Childrens Hospital, Singapore Professor Hui-Kim Yap National University of Singapore Professor Tsu-Fuh Yeh China Medical University, Taiwan
JPOG MAR/APR 2013 i
Navigating New Frontiers

EARLY BIRD REGISTRATION DEADLINE 30
The Changing Panorama of Womens Health:
Raffles City Convention Center Singapore

APRIL 2013
22-24 August 2013
www.sicog2013.com
Organised by Scientific Secretariat
Latest Programme & Registration at
M AR / APR Vol. 39
2013 No. 2
Review Article Obstetrics
49 Hypertension in Pregnancy Hypertension is a common complication of pregnancy and remains a major cause of maternal and perinatal
morbidity and mortality worldwide. Patients with hypertensive disorders of pregnancy warrant cautious care with consultant obstetric, neonatal and anaesthetic involvement to optimize both maternal and fetal outcomes. Fergus P McCarthy, Louise C Kenny
49
Review Article Paediatrics
61 Evaluation of the Acute Abdomen Evaluation of the acute abdomen in infants and children can be challenging. The authors review a
structured approach to assessment and define the management of some of the more serious acute abdominal conditions seen in children such as intussusception, appendicitis, and malrotation/volvulus. Erica Makin, Mark Davenport
61
Publisher
Ben Yeo
Publication Manager
Enquiries and Correspondence

China Yang Xuan Tel: (86 21) 6157 3888 Email: enquiry.cn@ubmmedica.com Hong Kong Kristina Lo-Kurtz, Jacqueline Cheung, Marisa Lam, Miranda Wong Tel: (852) 2559 5888 Email: enquiry.hk@ubmmedica.com India Monica Bhatia Tel: (91 022) 6612 2678 Email: enquiry.in@ubmmedica.com Korea Choe Eun Young Tel: (82 2) 3019 9350 Email: inquiry@kimsonline.co.kr Indonesia Hafta Hasibuan, Sri Damayanti, Ritta Pamolango Tel: (62 21) 729 2662 Email: enquiry.id@ubmmedica.com Malaysia Meera Jassal, Lee Pek Lian, Irene Lee, Grace Yeoh Tel: (60 3) 7954 2910 Email: enquiry.my@ubmmedica.com Philippines Marian Chua, Kims Pagsuyuin, Rowena Belgica, Philip Katipunan Tel: (63 2) 886 0333 Email: enquiry.ph@ubmmedica.com Singapore Jason Bernstein, Carrie Ong, Elijah Lee, Reem Soliman Tel: (65) 6290 7400 Email: enquiry.sg@ubmmedica.com Thailand Wipa Sriwijitchok Tel: (66 2) 741 5354 Email: enquiry.th@ubmmedica.com Vietnam Nguyen Thi Lan Huong, Nguyen Thi My Dung Tel: (84 8) 3829 7923 Email: enquiry.vn@ubmmedica.com Europe/USA Kristina Lo-Kurtz Tel: (852) 2116 4352 Email: enquiry.hk@ubmmedica.com
Marisa Lam Greg Town
Managing Editor Associate Editor
Grace Ling
Designers
Agnes Chieng, Sam Shum

Production
Edwin Yu, Ho Wai Hung, Steven Cheung

Circulation
Christine Chok
Accounting Manager
Minty Kwan Jenny Lim
Advertising Coordinator
Published by:
PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is published 6 times a year by UBM Medica, a division of United Business Media. CIRCULATION: JPOG is a controlled circulation for medical practitioners in South East Asia. It is also available on subscription to members of allied professions. SUBSCRIPTION: The price per annum is US$42 (surface mail, students US$21) and US$48 (overseas airmail, students US$24); back issues US$8 per copy. EDITORIAL MATTER published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great care has been taken in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. COPYRIGHT: 2013 UBM Medica. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, in any language, without written consent of copyright owner. Permission to reprint must be obtained from the publisher. ADVERTISEMENTS are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Philippine edition: Entered as second-class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee Chung Street, Chai Wan, Hong Kong.
UBM Medica Pacific Limited 27th Floor, OTB Building 160 Gloucester Road, Wan Chai, Hong Kong Tel: (852) 2559 5888 Email: enquiry@jpog.com
JPOG MAR/APR 2013 ii
PRINT ONLINE DIGITAL EDITION

Read Medical Tr ibune anytime, anywhere
December 2012
www.medicaltribune.com
Important benefits for women who quit smoking early

www.MIMS.com
Elvira Manzano
moking nearly triples the risk of premature death in women and quitting the habit well before middle-age reduces this risk, according to the Million Women Study. In this prospective study, the largest in the history of studying the dangers of smoking, 12-year mortality rates among women who smoked throughout their adult years were almost three times higher than those of women who never smoked (rate ratio 2.97, 95% CI, 2.88-3.07). Even light smokers (those who smoked fewer than 10 cigarettes per day) had twice the mortality rate of never-smokers (rate ratio 1.98, 95% CI, 1.912.04). [Lancet 2012.DOI.org/10.1016/S01406736(12)61720-6] What was encouraging, however, was the positive effect that quitting seemed to have on womens life span. Stopping the habit before age 40 avoided more than 90 percent of excess mortality from cigarettes. Quitting before age 30 avoided 97 percent of this added risk. Smokers who stop before reaching middle-age will on average gain about an extra 10 years of life, said study author Professor Sir Richard Peto, of the University of Oxford, Oxford, UK. This does not, however, mean that it is safe to smoke until age 40 and then stop, the authors warned. Decades later throughout life, women who smoked and stopped still have 1 to 2 times the mortality rate of neversmokers. For those who continued to smoke past age 40, the risk is 10 times greater. The study enrolled 1.3 million women (age 50-65) in the UK followed for 12 years. At baseline, 20 percent were smokers, 28 percent were former smokers and 52 percent never smoked.
Smart Rx. Every Time.
FORUM
Science and health policy: Lost in translation
02
philippine FOCUs
Women who quit smoking early can avoid a three-fold increased risk of death, according to the Million Women Study. By 2011, 66,000 had died. Compared with non-smokers, smokers lost at least 10 years of life and died from smoking-related diseases such as lung cancer, heart disease and stroke. While the absolute hazards of prolonged smoking are substantial, so are the benefits of quitting. Even cessation at about 50 years of age avoids at least two-thirds of the continuing smokers excess mortality in later middle age, the authors said. The benefits are, however, greater in those who quit earlier. In a linked comment, Dr. Rachel Huxley, from the University of Minnesota, Minneapolis, US, and Dr. Mark Woodward, from the University of Sydney, Australia, welcomed the findings. Aside from its impressive sample size, the Million Women Study is distinct from previous large cohortsand superior for assessment among women of the full hazards of prolonged smoking and the full benefits of long-term cessation because the participants were among the first generation of women in the UK in which smoking was widespread in early adult life, and although many continued smoking, many stopped before age 30 or 40 years. The results emphasize the need for effective sex-specific and culturally-specific tobacco control policies that encourage adult smokers to quit and discourage children and young adults from starting smoking, they concluded.
DOH releases advisory on stem cell therapies
03
COnFeRenCe
Multivitamins may protect against cancer

Rajesh Kumar
aily multivitamin use for more than a decade caused a modest but statistically significant 8 percent reduction in all cancers among men in a large randomized, double-blind, placebo control trial. Researchers analyzed data from the Physicians Health Study II involving 14, 641 male US physicians aged 50 years or older, including 1,312 men with a history of cancer. The men were randomized in 1997 to receive either multivitamin supplements or placebo
Monoclonal antibody aids statin-refractory patients
11
and were followed up through June 1, 2011. [JAMA 2012; DOI:10.1001/jama.2012.14641] The primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points. During the trial, 2,669 cases of cancer were detected, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer, with some men experiencing multiple events. Men taking a daily multivitamin had a statistically significant reduction in the in-
cidence of total cancer compared with those taking placebo (17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR] 0.92; 95% CI, 0.86-0.998; P=0.04). The multivitamin group had a similar reduction in total epithelial cell cancer, but not in other site specific cancers such as colorectal, lung and bladder cancer. The men who had a history of cancer at baseline also saw a reduction in their total cancer risk but this was not any different from the case of healthier men. Turn to page 2 >>
AFTeR hOURs
Malacca: A journey through time
18
Download Medical Tribune Digital Edition

Go to www.medicaltribune.com or Scan the QR code to download now!
M AR / APR Vol. 39
2013 No. 2
Review Article Gynaecology
74 The Management of Perimenopausal Menstrual Symptoms Abnormal bleeding around the time of the menopause is common and may be a sign of premalignancy
such as endometrial hyperplasia or even endometrial carcinoma. As such, all will need uterine assessment which may include transvaginal scan combined with endometrial biopsy, hysteroscopy or a sonohysterogram. Having excluded (pre) cancer, treatment can then be offered. John Eden, Sheila ONeill
P 3 SK
74
Continuing Medical Education
81 Imaging in Ectopic PregnancyRevisited Ectopic pregnancies are one of the leading causes of pregnancy-related first-trimester death. They remain
a significant gynaecological emergency, and delay in diagnosis and treatment can be catastrophic. Lam Shu Lin, Ong Chiou Li
81
The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under licence from UBM Media LLC. The articles appearing on pages 4953, and pages 6780 are reprinted with permission of Consultant for Pediatricians. Copyright 2011 UBM Media LLC. All rights reserved.
Review Articles
Comprehensive reviews providing the latest clinical information on all aspects of the management of medical conditions affecting children and women.
Case Studies
Interesting cases seen in general practice and their management.
The Cover: Perimenopausal Menstrual Symptoms 2013 UBM Medica
Pictorial Medicine
Vignettes of illustrated cases with clinical photographs.
For more information, please refer to the Instructions for Authors on our website www.jpog.com, or contact: The Editor UBM Medica Asia Pte Ltd, 6 Shenton Way, #15-08 Tower 2, Singapore 068809 Tel: (65) 6290 7400 Fax: (65) 6290 7401 E-mail: enquiry@jpog.com
Lisa Low, Illustrator
JPOG MAR/APR 2013 iii
JPOG is Now CME-Accredited...

in Hong Kong, Indonesia, Malaysia and Singapore
For over 35 years, JPOG has been the only regional, peer-reviewed journal of paediatrics, obstetrics and gynaecology in Asia. The bimonthly journal is proud to announce its CME-accreditation in the following Asian countries: HONG KONG, INDONESIA, MALAYSIA and SINGAPORE.
From the research bench to your patients bedside JPOG raises the quality of life of women and children in Asia. Pick up a copy today and start earning CME points. For further details, visit www.jpog.com today.
PEER REVIEWED
Journal Watch
reaching the primary end point (6.6% vs 10.5%),
tal deaths within 48 hours of birth; there was no significant association between maternal obesity and later neonatal deaths. In sub-Saharan Africa, maternal obesity is associated with increased neonatal mortality within 2 days of birth. Suggested mechanisms include prematurity, intrapartum events, and infections. Obese mothers should be advised to deliver in wellequipped units.
Cresswell A et al. Effect of maternal obesity on neonatal death in subSaharan Africa: multivariable analysis of 27 national datasets. Lancet 2012; 380: 13251330; Nohr EA. Maternal obesity and neonatal mortality in an African setting. Ibid: 12921293 (comment).
GYNAECOLOGY
and mortality was non-significantly 34% less in the HRT group (5.4% vs 7.9%). There was no significant difference in the rate of stroke between the
HRT and cardiovascular risk in early menopause
two groups (2.2% vs 2.8%) or in the rate of venous thromboembolism, which was low in both groups. The groups did not differ significantly in the incidence of breast or other cancers. The rate of death or breast cancer was significantly 46% lower in the HRT group (4.4% vs 7.9%). HRT begun early in the menopause reduced cardiovascular risk without increasing the risks of cancer or thromboembolism.
Schierbeck LL et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012; 345 (Nov 3): 16 (e 6409).
Comparing drugs for tocolytic therapy

A systematic review and network meta-analysis had addressed the question of which are the best
OBSTETRICS
agents for delaying delivery when preterm birth is threatened. The study included 95 randomized controlled
Maternal obesity and neonatal death in Africa

There is controversy about the risks and benefits of hormone replacement therapy (HRT) during the menopause. Now, a study in Denmark has shown that HRT begun early in the menopause protects against heart disease. The trial was primarily aimed at investigating the effect of HRT on osteoporosis. A total of 1,006 recently postmenopausal or perimenopausal women aged 4558 were randomized to HRT with 17- -estradiol plus norethisterone acetate (or 17- -estradiol alone if post-hysterectomy) or no treatment, for about 11 years. The primary end point (death, myocardial infarction, or heart failure) was reached by 3.2% (HRT) vs 6.5% (controls), a significant 52% reduction in the HRT group. There was a non-significant 43% reduction in mortality with HRT. After 16 years of follow-up, there was still a significant difference in the proportions Overweight and obesity have become more common in developing countries. The children of obese mothers are more likely to die perinatally, to be admitted to the neonatal intensive care unit, to be macrosomic, and to have low Apgar scores. Data from 27 countries in sub-Saharan Africa have illustrated the dangers of maternal obesity. Pooled data from cross-sectional Demographic and Health Surveys from the 27 countries were analysed. Of 81,126 women, 15,518 (19%) were overweight, among whom 4,266 (5% of the total) were obese, 52,006 (64%) were of normal weight, and 13,602 (17%) were underweight. Maternal obesity (body mass index, 30 kg/m 2 or higher) was associated with a 46% increase in risk of neonatal death in a singleton live birth in the previous 5 years. This increased risk was entirely for neona-
trial. Compared with placebo, the odds ratio for delay of delivery by 48 hours was 5.39 for prostaglandin inhibitors, 2.76 for magnesium sulfate, 2.71 for calcium-channel blockers, 2.41 for beta mimetics, and 2.02 for atosiban (an oxytocin receptor blocker). Tocolytics did not reduce the risk of neonatal respiratory distress syndrome. Side effects leading to a change of medication were more likely with beta mimetics, magnesium sulfate, or calciumchannel blockers. Overall, prostaglandin inhibitors and calcium-channel blockers were perhaps the most effective drugs. Prostaglandin inhibitors and calcium-channel blockers appear to be the most effective tocolytics, but whether delaying delivery is beneficial for the baby remains a valid question.
Haas DM et al. Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ 2012; 345 (Oct 20): 17 (e6226); Alfirevic Z. Tocolytics: do they actually work? Ibid: 7(e6531) (editorial).
JPOG MAR/APR 2013 45
Single progesterone level to detect non-viability of early pregnancy
Verhaegen J et al. Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies. BMJ 2012; 345 (Oct 20): 18 (e6077).
Changes in money given for maternal, newborn, and child health in Countdown countries
PAEDIATRICS
Equity in maternal and child health interventions

As countries strive to reach Millennium Development Goals (MDGs) for maternal and child health, effective interventions have been increased. Takeup of these interventions is often greater in more prosperous communities, leading to inequalities in coverage. Progress towards MDGs is monitored in 75 countries by the Countdown to 2015 collaboration, these countries accounting for > 95% of all For women with bleeding or pain in early pregnancy, a single progesterone test may indicate non-viability, according to a recent meta-analysis. The analysis included 26 cohort studies (9,436 women), 19 studies of women with symptoms alone, and seven of women with both symptoms and inconclusive ultrasound assessment. Among women with symptoms and inconclusive ultrasound findings, a progesterone test (cut-off values, 3.26.0 ng/mL) had a sensitivity of 74.6% and a specificity of 98.4% for a non-viable pregnancy (positive likelihood ratio, 45; negative likelihood ratio, 0.26). The overall median prevalence of non-viable pregnancy was 73.2%, and the probability increased to 99.2% with a low progesterone level. For women with symptoms alone and using a 10 ng/mL threshold, the sensitivity was 66.5% and specificity 96.3% (positive likelihood ratio, 19; negative likelihood ratio, 0.35). The overall probability of non-viable pregnancy was 62.9%, increasing to 96.8% with a low progesterone level. A single progesterone test for symptomatic women in early pregnancy can rule out viability. maternal and child deaths. Now, repeated surveys in 35 countries have been used to assess the relationship between increased intervention coverage and equity. Data were obtained from 35 Countdown countries with two surveys done at an average interval of 9.1 years. Although the rich often had greater coverage, increased coverage for skilled birth attendants, measles vaccination, and an increase in a composite coverage index were associated with improved equity. For use of insecticide-treated bed nets by children, countries achieving rapid progress reached rich and poor almost equally. National increases in coverage were mainly due to increased coverage among the poor. Equity needs to be taken into account as well as total coverage in assessing progress to MDGs.
Victoria CG et al. How changes in coverage affect equity in maternal and child health interventions in 35 Countdown to 2015 countries: an analysis of national surveys. Lancet 2012; 380: 11491156; Bhutta ZA, Chopra M. The Countdown for 2015: what lies ahead? Ibid: 11251127 (comment).
The global financial crisis may be affecting funding for Millennium Development Goals 4 and 5. As part of Countdown to 2015, recent changes in official development assistance (ODA) to maternal, newborn, and child health have been assessed in 74 Countdown priority countries. Since 2003, giving to maternal, newborn, and child health increased in all countries up to US$6,511 million in 2009 but fell slightly for the first time to US$6,480 million dollars in 2010. The rate of increase in ODA for maternal and child health has decreased since 2008. Targeting of ODA to countries with high maternal mortality increased between 2005 and 2010, as did targeting to child health but to a lesser extent. ODA may have slowed as a result of the global financial crisis.
Hsu J et al. Countdown to 2015: changes in official development assistance to maternal, newborn, and child health in 200910, and assessment of progress since 2003. Lancet 2012; 380: 11571168; Horton R. Womens and childrens health: no time for complacency. Ibid: 11231125 (comment).
PEER REVIEWED
Journal Watch
MDG 4 success of Niger
in stunting. Child survival interventions such as insecticide-treated bed nets, improved nutrition, vitamin A supplementation, appropriate treatment of diarrhoea, improved care seeking for fever, malaria, or pneumonia, and vaccinations all improved. Several programme strategies have been important in Nigers success: high government priority for universal access to free primary health care for women and children, mass campaigns for insecticide-treated bed nets, measles vaccination and vitamin A supplementation, and an attack on child undernutrition.
Amouzou A et al. Reduction in child mortality in Niger: a countdown to 2015 country case study. Lancet 2012; 380: 11691178; Sanda S. Nigers success in child survival. Ibid: 11271128 (comment).
BMI and cardiovascular risk factors in children
Only 23 of 74 Countdown countries look like achieving Millennium Development Goal (MDG) 4 (a two-thirds reduction in under-5s mortality between 1990 and 2015). Niger is ranked 186 of 187 countries on the Human Development Index and the average woman has seven children. Although total official development assistance (ODA) fell between 2003 and 2008, ODA to maternal and child health increased considerably with a threefold increase in funding per live birth and almost sixfold increase per child. Data now show that Niger has achieved remarkable reductions in child mortality. Mortality in children < 5 years old fell by 43% from 226 deaths per 1,000 live births in 1998 to 128 in 2009, a rate of decrease of 5.1% per year, although neonatal mortality remained high. Achieving MDG 5 needs an annual fall of 4.3% in under-5s mortality. The improvement in Niger has far exceeded those in neighbouring countries (Benin, 2.2% per year; Burkina Faso, 0.8%; Chad, 0.9%; Mali, 1.8%; Nigeria, 2.0%). The prevalence of wasting decreased by about 50% over the same period although there was only a slight decrease
Clinicians gut feeling about serious infection in children

Serious infections in children may easily be missed on clinical examination with potentially disastrous results. Routine clinical assessment may be normal, but the doctor may be left with a gut feeling that all is not well. A study in general practice has shown the value of gut feeling. The study included 3,369 children presenting with an acute illness that had lasted for up to 5 days. Among children in whom other features did not cause concern, a gut feeling that the child was unwell increased the risk of serious infection by a factor of 25. It had a sensitivity of 33% and a specificity of 99%. The gut feeling was most often based on decreased conscious level, tachypnoea, or parental concern. Clinicians should take their gut feelings seriously.
Van den Bruel A et al. Clinicians gut feeling about serious infections in children: observational study. BMJ 2012; 345: (Sept 29): 14 (e6144).
A systematic review and meta-analysis has suggested that a high body mass index in childhood is more strongly associated with cardiovascular risk factors than previously thought. The analysis included 63 studies of children aged 515 years in developed countries (49,220 children). Among overweight children, systolic blood pressure was raised by an average of 4.54 mm Hg compared with children with a normal body mass index. Among obese children, the rise of systolic blood pressure was 7.49 mm Hg. The average increases in diastolic blood pressure were 2.57 and 4.06 mm Hg, respectively. Obesity was also associated with significant increases in total serum cholesterol and low-density lipoprotein cholesterol. Both overweight and obesity were significantly associated with increases in fasting insulin levels, insulin resistance, increased triglycerides, and decreased high-density lipoprotein cholesterol levels. Overweight and obese children may be at increased cardiovascular risk in later life.
Friedemann C et al. Cardiovascular disease risk in healthy children and its association with body mass index: systematic review and meta-analysis. BMJ 2012; 345: (Sept 29) 15 (e4759); Hudson L, Viner RM. Obesity in children and adolescents. Ibid: 8 (e5457) (editorial).
Metcalf B et al. Effectiveness of interventions on physical activity of children: systematic review and meta-analysis of controlled trials with objectively measured outcomes. BMJ 2012; 345 (Sept 29): 16 (e5888); Hamer M, Fisher A. Are interventions to promote physical activity in children a waste of time? Ibid: 9 (e6320) (editorial).
tervention group. Reduced intake of sugar-sweetened drinks was associated with reduced weight gain in normal-weight Dutch children aged 512 years.
Physical activity interventions in children
In American overweight and obese adolescents,
High-sugar drinks and body weight in children and adolescents

High intake of sugar-sweetened drinks has been associated with increased body mass index (BMI) in children. Two studies reported in the New England Journal of Medicine have shown that reducing the intake of sugar-sweetened drinks may reduce levels of obesity and overweight in children and adolescents. In Amsterdam, the Netherlands, an 18-month double-blind trial included 641 normal-weight children aged 4 years 10 months to 11 years 11 months at eight schools. Randomization was to receive 250 mL on each school day and at weekends of either
a 1-year programme of reduced intake of sweetened drinks was associated with reduced increase in BMI at the end of the intervention but not 1 year later. Several US organizations have called for measures to reduce the consumption of sugarsweetened drinks in children and adults.
de Ruyter JC et al. A trial of sugar-free or sugar-sweetened beverages and body weight in children. NEJM 2012; 367: 13971406; Ebbeling CB et al. A randomised trial of sugar-sweetened beverages and adolescent body weight. Ibid: 14071416; Caprio S. Calories from soft drinks do they matter? Ibid: 14621463 (editorial).
Classroom-based CBT for adolescents at risk of depression: Not effective

There is evidence that classroom-based cognitive behavioural therapy (CBT) might prevent depression in some adolescents, but there has been no rigorous study. Now, a study in eight schools in the UK has shown no effect from classroom-based CBT. The study included 5,030 school students aged 1216 years, among whom 1,064 (21%) were identified as at high risk of depression. Outcome data were available for 846 (80%) of the at-risk group. Randomization was to classroom-based CBT, attention control, or usual provision. At 12 months, adjusted mean scores on the short mood and feelings questionnaire were similar in the three groups. Reported self worth and anxiety were not significantly different between groups. There was a small increase in negative thoughts in the CBT group. Classroom-based CBT did not reduce symptoms of depression in at-risk adolescents.
Stallard P et al. Effect of classroom based cognitive behavioural therapy on symptoms of depression in high-risk adolescents: pragmatic cluster randomised controlled trial. BMJ 2012; 345 (Oct 13): 13, (e6058); Merry SN, Stasiak K. Preventing depression in adolescents. Ibid: 8 (e6720) (editorial).
Encouraging more physical activity in children seems instinctively to be a worthwhile endeavour. Current UK guidelines suggest at least 60 minutes of moderate to vigorous exercise a day for all children and adolescents, but few achieve it and activity levels tend to drop off in adolescence. A systematic review and meta-analysis has illustrated the difficulties in encouraging exercise. The analysis included 30 studies (6,153 children) with physical activity measured by accelerometer throughout the day at baseline and followup. The pooled intervention effect was small to negligible for total physical activity and small for moderate or vigorous physical activity. It equated to an extra 4 minutes of walking and running per day. The effects of the physical activity interventions were small or negligible. Editorialists insist that research should continue with the aim of finding more effective interventions.
a sugar-containing drink with 104 kcal or an artificially sweetened, sugar-free, calorie-free drink. The BMI z score increased by a mean of 0.15 SD units (sugar) and 0.02 SD (sugar-free), a significant difference. The increase in weight was 7.37 kg vs 6.35 kg, also a significant difference. There were also significant reductions in increase of skinfold thickness, waist-to-height ratio, and fat mass in the sugar-free group. A US study included 224 overweight or obese adolescents (mean age, 15 years). Randomization was to an intervention group (multicomponent intervention to reduce consumption of sugarsweetened drinks with provisions of non-calorie drinks, motivational telephone calls, and check visits) or a control group, for 1 year of intervention and a further year of follow-up. At 2 years, there was no significant difference in change in BMI between the two groups. At 1 year, however, the change in BMI was 0.57 kg/m 2 less in the in-
OBSTETRICS OBSTETRICS
II
PEER PEER REVIEWED REVIEWED
Perinatal Case Management Caring for Mothers as They Care Hypertension in Pregnancy for Babies
Fergus P McCarthy, MSc, PhD, MRCPI; Louise C Kenny, PhD, MRCOG Chng Ying Chia, MA (Applied Social Studies); Jemie Biwen Wang, Bachelor of Psychology (Hons); Helen Chen, MBBS, M Med (Psych), Dip. Psychotherapy
INTRODUCTION
Hypertension is a frequently encountered complication of pregnancy and has a number of possible aetiologies. In the United Kingdom, the number of maternal deaths from hypertension in pregnancy has fallen steadily over the past few decades, as have the complication rates. However, hypertensive disorders remain a major cause of maternal and perinatal morbidity and mortality worldwide. Interventions to prevent hypertensive disorders in pregnancy including pre-eclampsia in the general population have been disappointing, and the mainstay of treatment involves close antenatal supervision of mother and fetus and timely delivery to prevent deterioration of the condition and subsequent morbidity and mortality.
HYPERTENSION IN PREGNANCY
Classification and Diagnosis of Hypertension The classification of hypertension in pregnancy by Davey et al remains the most widely accepted and appropriate classification (Box 1). Women who are hypertensive and pregnant must be subdivided into those with: chronic hypertension pregnancy-induced or gestational hypertension. Women with pregnancy-induced hypertension are subdivided further: the majority have non-proteinuric pregnancy-induced hypertension, a condition associated with minimal maternal or perinatal mortality/morbidity a minority have the major pregnancy complication of pre-eclampsia. Pre-eclampsia is associated with significant maternal and perinatal morbidity
OBSTETRICS
PEER REVIEWED
Box 1. Classification of hypertension in pregnancy
A. New-onset hypertension and/or proteinuria in pregnancy 1. Gestational hypertension (without proteinuria) 2. Gestational proteinuria (without hypertension) 3. Pre-eclampsia (hypertension with proteinuria) B. Chronic hypertension and renal disease 1. Chronic hypertension without proteinuria 2. Chronic renal disease (proteinuria with or without hypertension) 3. Chronic hypertension with superimposed pre-eclampsia (ie, with new-onset proteinuria in pregnancy) C. Unclassified 1. Hypertension and/or proteinuria noted when first presentation is after 20 weeks 2. As above, when noted for the first time during pregnancy, labour or puerperium, and there are insufficient backgro und data to permit a diagnosis from category A or B above
Pregnancy-induced Hypertension Gestational or pregnancy-induced hypertension is a rise in the blood pressure in the absence of proteinuria after 20 weeks gestation. True non-proteinuric pregnancy-induced hypertension does not appear to be associated with an increase in maternal or fetal morbidity. However, the risk of progression from pregnancy-induced hypertension to pre-eclampsia is approximately 2030% and therefore vigilance is required. This rate increases to approximately 50% when pregnancy-induced hypertension develops before 32 weeks gestation. As a result of this risk of progression to pre-eclampsia, weekly urinalysis and blood pressure checks are generally recommended in women with pregnancy-induced hypertension. Chronic Hypertension Chronic hypertension is defined as hypertension preceding pregnancy. Blood pressure falls in the first and second trimesters. Therefore, women with high blood pressure before the 20th week of pregnancy are assumed to have pre-existing or essential hypertension. As many women of reproductive age only present for the first time when pregnant, chronic hypertension is often revealed in the first half of pregnancy. Approximately 9095% of cases of chronic hypertension are considered to be essential. Secondary causes which account for approximately 510% are listed in Table 1. In women presenting with hypertension in the first half of pregnancy, it is important to look for an underlying cause. These investigations should at least include: urine analysis (looking for blood, protein or glucose) urea and electrolytes renal tract ultrasound. Women with underlying renal disease are at significantly increased risk of poor pregnancy outcome and require multidisciplinary care.
and mortality. As such, it is imperative that every effort is made to accurately classify women with hypertension in pregnancy as having chronic hypertension, non-proteinuric pregnancy-induced hypertension or pre-eclampsia, as the aetiology and management of the three conditions is very different.
Measurement of Blood Pressure Blood pressure should be measured with the woman rested and seated at a 45-degree angle with the arm at the level of the heart. It is imperative that an appropriately sized cuff should be used. To avoid incorrect measurement of blood pressure, if the midarm circumference is greater than 33 cm, a large cuff should be used. Korotkoff phase 1 should be used to measure systolic blood pressure, and Korotkoff 5 is the appropriate measurement of diastolic blood pressure. The method used to record blood pressure should be consistent and documented.
OBSTETRICS
PEER REVIEWED
Treatment of Chronic Hypertension in Pregnancy The use of antihypertensive drugs in the hypertensive women without renal impairment is considered by some to be beneficial in preventing sudden increases in blood pressure, cerebral haemorrhage or hypertensive encephalopathy. However, a clear benefit of antihypertensive agents in mild-to-moderate chronic hypertension remains unproven, as treatment does not prevent placental abruption or superimposed pre-eclampsia, or influence perinatal outcome. There are differing opinions regarding the timing of initiation of treatment in hypertensive disorders in pregnancy. This is compounded by the fact that a single blood pressure of 140/90 mm Hg or above is not uncommon in pregnancy and was reported in nearly 40% of pregnant women in one study, while persistent high blood pressure occurs in approximately 1222% of pregnancies. Until recently, the focus remained on treating elevated blood pressure based on the diastolic reading with groups recommending treatment for sustained diastolic blood pressures of greater than 105110 mm Hg. There is now however increasing awareness on the importance of increases in, as well as the absolute values of, systolic blood pressure. Generally, the aim of antihypertensive therapy in women without underlying medical problems is to keep the systolic blood pressure at 130155 mm Hg and diastolic blood pressure at 80105 mm Hg. Both Centre for Maternal and Child Enquiries (CMACE) 20062008 and National Institute for Health and Clinical Excellence (NICE) clinical guideline on hypertension in pregnancy recommend that all pregnant women with a systolic blood pressure of 150 mm Hg or more require antihypertensive treatment. Consideration should also be given to initializing treatment at lower pressures if the overall clinical picture suggests rapid deterioration and/ or where the development of severe hypertension
Table 1. Causes of secondary chronic hypertension Idiopathic Vascular disorders Endocrine disorders Essential hypertension Renovascular hypertension Aortic coarctation Diabetes mellitus Hyperthyroidism Hypothyroidism Phaeochromocytoma Acromegaly Cushings syndrome Conns syndrome Renal failure resulting from: Diabetic nephropathy Reflux nephropathy Chronic glomerulonephritis Nephritic and nephrotic syndrome Polycystic kidney Systemic lupus erythematosus Systemic sclerosis Polyarteritis nodosa Rheumatoid disease
Renal disorders
Connective tissue disorders
can be anticipated. In the 20062008 CMACE report, particular emphasis was placed on the implementation of effective antihypertensive treatment in women with systolic blood pressures greater than 150 mm Hg. A systolic blood pressure greater than 180 mm Hg should be considered a medical emergency, and quick effective treatment is advocated to prevent haemorrhagic stroke. Women with chronic hypertension taking ACE inhibitors or angiotensin II receptor blockers should be counselled that there is an increased risk of congenital abnormalities if these drugs are taken during pregnancy. There are multiple alternative antihypertensive agents available which may be used in pregnancy. These can be used independently or
OBSTETRICS
PEER REVIEWED
Table 2. Numbers of direct deaths attributed to eclampsia and pre-eclampsia and mortality rates per 100,000 maternities; United Kingdom: 19852008 Triennium 198587 198890 199193 199496 199799 200002 200305 200608
CI = confidence interval.
mencing treatment and may return after increasing the dose. Use of the long-acting oncedaily preparation improves compliance. Nifedipine is a potent antihypertensive agent and should not be given sublingually as it may cause a precipitate fall in blood pressure, which can lead to fetal distress. agonist that inhibits vasoconstricting impulses from the medulla oblongata) has traditionally been the most commonly used agent for the control of blood pressure during pregnancy. Its safety has been well established both in pregnancy and in the long-term follow-up of the infants. One of the most frequent side effects is sedation, which can be profound. This is often poorly tolerated and leads to unpredictable compliance. However, -methyldopa remains the preferred agent of the National High Blood Pressure Education Programme. ACE inhibitors and angiotensin receptor blockers and diuretics should be avoided in pregnancy. Diuretics may reduce uteroplacental Second- and third-trimester exposure to ACE
Number 27 27 20 20 16 14 18 19
Rate 1.19 1.14 0.86 0.91 0.75 0.70 0.85 0.83 0.82 0.79 0.56 0.59 0.46 0.42 0.54 0.53
95% CI 1.73 1.66 1.33 1.41 1.22 1.18 1.35 1.30
-Methyldopa (a centrally acting -adrenergic
in conjunction with a second or third agent. Labetalol is a popular first-line antihyperten

sive of choice in the treatment of hypertension. Labetalol is a combined -adrenoceptor blocker that also blocks -adrenoceptors. Orfor producing a quick antihypertensive effect because a quick fall in blood pressure triggers a compensatory sympathetic discharge thatincreasestheperipheralvascularresistancevia-adrenoceptors.Blocking this compensatory response, but the addition of an -adrenoceptor blocker can. It is this action that renders labetalol suitable for gaining quick control of the blood pressure. Labetalol, like all -adrenoceptors, is contraindicated in women with a history of asthma. the treatment of chronic hypertension in pregnancy. Data suggest that it is safe, but cumulative evidence is not as extensive as with older drugs such as labetalol and methyldopa. The principal side effect is headache, which can be severe, lasts for several days after com
dinary -adrenoceptor blockers are unsuitable
perfusion. inhibitors appears to be fetotoxic, producing fetal hypocalvaria and renal defects. The cause of these defects seems to be related to fetal hypotension and reduced renal blood flow. Anuria associated with oligohydramnios can produce fetal limb contractures, craniofacial deformations and pulmonary hypoplasia. Intrauterine growth restriction, prematurity, persistence of a patent ductus arteriosus, severe neonatal hypotension, neonatal anuria, and neonatal or fetal death have all been observed with use of these drugs, and they should therefore be discontinued preconceptually or as early in the first trimester as possible. Angiotensin receptor blockers are newer agents that have not been formally studied in pregnancy; they are probably best
the -adrenoceptors alone cannot prevent
Nifedipine is a calcium channel blocker used in
OBSTETRICS
PEER REVIEWED
avoided given their common pathway with ACE inhibitors.
Table 3. Risk factors for pre-eclampsia Risk factor Unadjusted relative risk (95% confidence interval) 1.68 (1.232.29) 1.96 (1.342.87) 2.90 (1.704.93) 2.91 (1.286.61) 2.93 (2.044.21) 3.56 (2.544.99) 4.29 (3.525.49) 7.19 (5.858.83) 9.72 (4.3421.75)
PRE-ECLAMPSIA
Introduction Pre-eclampsia is a potentially life-threatening hypertensive disorder of pregnancy characterized by vascular dysfunction and systemic inflammation involving the brain, liver, and kidneys of the mother. The incidence of pre-eclampsia has risen in countries such as the United States of America, but maternal mortality from pre-eclampsia has decreased significantly in the UK since 1992 (Table 2).
Age 40 years, primiparae Age 40 years, multiparae Family history Nulliparity Multiple pregnancy Pre-existing diabetes Pre-pregnancy body mass index 35 Previous pre-eclampsia Antiphospholipid syndrome
common in primigravid women as in women having
Pre-eclampsia is twice as common in primigravid women as in women having second or later pregnancies
second or later pregnancies. Women who become pregnant with donor eggs are at increased risk of developing pre-eclampsia while particular men are at increased risk of fathering a pre-eclamptic pregnancy. Table 3 highlights other risk factors for preeclampsia. Pre-eclampsia also carries implications in adult life, with offspring of affected pre-eclamptic pregnancies demonstrating poor growth in childhood and an increased risk of hypertension, heart
Pre-eclampsia is defined by the International Society for the Study of Hypertension in Pregnancy as gestational hypertension of at least 140/90 mm Hg on two separate occasions measured at least 4 hours apart, accompanied by significant proteinuria of at least 300 mg in a 24-hour collection of urine, arising de novo after the 20th week of gestation in a previously normotensive woman and resolving completely by the 6th postpartum week. It usually occurs during the second half of pregnancy and complicates 28% of pregnancies, depending on population studied. Pre-eclampsia is twice as
disease and diabetes.
Pathophysiology of Pre-eclampsia Pre-eclampsia is thought to result from a combination of impaired trophoblast differentiation and invasion during the first trimester resulting in the failure of trophoblast cells to destroy the muscularis layer of the spiral arterioles resulting in the development of a poorly perfused placenta. However, this reduced placental perfusion alone is not sufficient to cause the maternal syndrome of pre-eclampsia, and it is thought that this process
OBSTETRICS
PEER REVIEWED
Women with pregnancy-induced hypertension need to be closely monitored with weekly urinalysis and blood pressure checks.
requires the influence of additional maternal factors including genetic make-up and environmental factors (such as obesity and diet), which together results in widespread endothelial dysfunction and hypertension.
Investigations and monitoring of the suspected pre-eclamptic patient should include: Full blood count: this may demonstrate a raised haematocrit (indicating haemoconcentration) and thrombocytopenia (which is an indicator of severe pre-eclampsia). Thrombocytopenia may also occur as a result of HELLP syndrome (haemolysis, elevated liver enzymes and low plate-
Management of Pre-eclampsia Ideally, women at high risk of pre-eclampsia should be reviewed pre-conceptually and advised to take 75 mg of aspirin daily from 12 weeks gestation until the birth of their child. Women considered at high risk of pre-eclampsia include those with any of the following: hypertensive disease during a previous preg nancy chronic kidney disease autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome type 1 or type 2 diabetes chronic hypertension.
lets). Urea and electrolytes: uric acid is a particularly sensitive measure of pre-eclampsia and perinatal outcome, but it is only of clinical significance if the levels are increasing or are very
high. If the platelet count is normal, it is not neces sary to perform a coagulation screen (prothrombin time, activated partial thromboplastin time and international normalized ratio) in cases of non-severe pre-eclampsia and gestational hypertension.
OBSTETRICS
PEER REVIEWED
Automated blood pressure devices may underestimate the blood pressure in women who are pregnant.
Urine analysis with a 24-hour urine collection or protein creatinine ratio. Significant proteinuria is the most important clinical variable predicting both maternal and perinatal outcome. All pregnant women should be assessed for proteinuria. Urinary dipstick testing may be used for screening for proteinuria when the suspicion of pre-eclampsia is low. The degree of positivity on urine dipstick correlates with the quantity of proteinuria as follows: 1+ = 0.3 g/L, 2+ = 1 g/L and 3+ = 3 g/L. Considerable observer error may occur with visual dipstick assessment, and this may be overcome by the use of automated dipstick readers, which significantly improve both false-positive and -negative rates. A reading of 1+ or more should prompt further evaluation. Clinically significant proteinuria is defined as a 24-hour urine protein excretion of 0.3 g and is based on a 95% confidence interval for urinary protein in pregnancy. An
elevated protein to creatinine ratio of greater than 30 mg/mmol correlates with a 24-hour urine excretion greater than 300 mg and may be used to check for significant proteinuria. Ultrasound: increased fetal surveillance with ultrasound assessment to evaluate fetal weight, progression of fetal growth, amniotic fluid index, and umbilical artery Doppler velocimetry should be performed at the time of diagnosis of pre-eclampsia once every 4 weeks thereafter with more frequent monitoring if any parameters are abnormal. The pharmacological treatment of pre-eclampsia focuses on controlling maternal hypertension. No drugs in current clinical use beneficially affect the human placenta. As a result, management involves treatment of maternal hypertension and close antenatal supervision of the mother and fetus with timely delivery to prevent deterioration of the mother and fetus. Pre-eclampsia can occaJPOG MAR/APR 2013 55
OBSTETRICS
PEER REVIEWED
sionally be managed conservatively. Maternal and fetal monitoring should continue until fetal maturity has been achieved, at which stage the cervix is assessed with Bishops scoring and, if favourable, induction of labour is carried out. Patients with pregnancy-induced hypertension may be monitored through a combination of general practitioners and hospital day care units. Severe pre-eclampsia necessitates inpatient care with a close monitoring of the symptoms, signs and biochemical parameters. No one definition defines 'severe' pre-eclampsia. However, the following features generally indicate the development of severe pre-eclampsia: Eclampsia Severe hypertension, eg, a systolic blood presure over 160 mm Hg with at least 2+ proteinuria Moderate hypertension associated with any of: severeheadachewithvisualdisturepigastric pain signs of clonus liver tenderness platelet count falling to below 100 10 /L
9
and vaginal delivery. Caesarean section is a better option for rapid deteriorating maternal and fetal condition, or alternatively for those remote from term with an unfavourable cervix. Epidural analgesia may be beneficial by preventing the increase of catecholamine release, in order to prevent further elevations of blood pressure during uterine contractions. It may also allow a more controlled second stage. Evidence from the HYPITAT trial suggests that women with gestational hypertension and nonsevere pre-eclampsia should be induced after 37 weeks gestation. This was associated with a significant reduction in adverse maternal outcome including progression to pre-eclampsia. Furthermore, no differences were observed in neonatal outcomes or caesarean section rates. Oral antihypertensive are discussed above. In severe pre-eclampsia, there are two antihypertensive regimens to choose from: Labetalol (200 mg) can be given orally prior to or in the absence of intravenous access; if there is no response within 30 minutes, a second oral dose can be given. If there is no initial response to oral therapy or if it is not tolerated, a bolus of 50 mg given intravenously over at least 5 minutes can be administrated, repeated to a maximum of 200 mg, at 10-minute intervals. Following this, or as treatment for moderate hypertension, a labetalol infusion can be commenced (5 mg/mL at 4 mL/h via a syringe pump, the infusion rate being doubled every 30 minutes to a maximum of 32 mL [160 mg]/h until the blood pressure has dropped and stabilized at an acceptable level). Labetalol is contraindicated in women with asthma and should be used with caution in cardiac
bance
creatinine 100 mmol/L 50 IU/L.
alanine aminotransferase rising to above
In extreme prematurity, transfer to hospital with adequate neonatal facilities (with steroid administration to enhance lung maturity) is indicated. Severe pre-eclampsia presenting prior to fetal viability is an indication for termination of pregnancy. The optimum time of delivery is of crucial importance and remains a balance between the risks of major complications to the mother and intrauterine growth retardation in the fetus against the risks of delivery and prematurity to the fetus. The mode of delivery is a balance between caesarean section
disease. Hydralazine is given by bolus infusion (10 20 mg over 1020 minutes measuring the blood pressure every 5 minutes). This may be fol-
OBSTETRICS
PEER REVIEWED
Box 2. Management of hypertension in pregnancy
Screening Women should be screened for signs of hypertension using blood pressure checks and urinalysis monthly until 30 weeks gestation, fortnightly from 30 weeks gestation and weekly from 36 weeks gestation If elevated blood pressure +/ proteinuria, refer for admission or monitoring in antenatal day unit Maternal assessment Repeat (at least 4-hourly) blood pressure measurement Quantitative measurement of protein in urine (pre-eclampsia = 0.3 g protein 24-hour urine collection) Platelet count, serum uric acid concentration, and tests of liver function (alanine and aspartate aminotransferase levels) Coagulation screen if altered liver function Antihypertensive therapy Consider admission, monitor closely and treat if blood pressure is persistently above 160/100 mm Hg Anticonvulsant therapy If convulsions occur, use magnesium sulphate, intravenously or intramuscularly In cases of severe pre-eclampsia, consider prophylactic magnesium sulphate Fetal management Give prophylactic steroids if the duration of gestation is less than 34 weeks Perform an ultrasound assessment of fetal weight on initial presentation and repeat fortnightly Doppler ultrasonographic assessment of umbilical blood-flow velocity if evidence of growth restriction Regular cardiotocography (non-stress tests) Ultrasonography at least twice a week for liquor volume Multidisciplinary approach regarding timing and mode of delivery Postpartum care Continued close monitoring of the mother by experienced carers If on magnesium therapy, continue for at least 24 hours post partum until stable Careful fluid balance (total 80 mL/h intake) and early use of diuretics if pulmonary oedema secondary to fluid overload is suspected Decrease dose of antihypertensive agents as indicated. Avoid sudden cessation immediately post partum as rebound hypertension likely Follow-up Long-term follow-up to make sure that the blood pressure falls (within 6 weeks post partum), and suitable referral if it does not Discussion about the illness and the significance for the future Recommend pre-conceptual counselling for future pregnancies
OBSTETRICS
PEER REVIEWED
Box 3. Key points in the management of the severe pre-eclamptic patient
lowed by an infusion (40 mg hydralazine in 40 mL normal saline, which should run at 1 5 mL/h [15 mg/h]). Management of hypertension is summarized in Box 2. In pre-eclampsia, magnesium sulphate is indi-
Insert an indwelling catheter and measure hourly urine output until stable Record blood pressure and pulse every 15 minutes until stable and then half hourly Oxygen saturation should be measured continuously and charted with the blood pressure. If saturation falls below 95%, then medical review is essential to outrule pulmonary oedema and other complications Strict fluid balance should be recorded with detailed input and output measurements Respiratory rate should be measured hourly. A reducing respiratory rate may indicate magnesium toxicity Temperature should be measured 4-hourly When present, central venous pressure and arterial lines should be measured continuously and charted with the blood pressure Neurological assessment should be performed hourly using either the AVPU (alert/verbal/painful/ unresponsive) or Glasgow Coma scales Fetal well-being should be monitored using a cardiotocography Blood tests should be repeated at least every 12 hours whilst on the magnesium sulphate protocol. In the event of complications such as haemorrhage or abnormal or deteriorating haematological and/or biochemical parameters, more frequent blood tests should be taken, eg, every 48 hours
cated as the first-line anticonvulsant. Formal clinical review should occur every 4 hours, observing for side effects (motor paralysis, absent reflexes, respiratory depression and cardiac arrhythmia). The antidote is 10 mL 10% calcium gluconate given slowly intravenously. Of the magnesium sulphate, 97% is excreted in the urine. Oliguria (< 80 mL per 24 hours) can thus lead to toxicity. Therefore, in the presence of oliguria, magnesium sulphate should be reduced or withheld. If magnesium is not excreted, levels should not fall. Box 3 highlights key management steps in the treatment of patients with severe pre-eclampsia.
Evidence from the HYPITAT trial suggests that women with gestational hypertension and non-severe pre-eclampsia
Box 4. Diagnostic criteria used for eclampsia
should be induced after 37 weeks gestation
Any woman with convulsion(s) during pregnancy or in the first 10 days post partum, together with at least two of the following features within 24 hours of the convulsion(s): Hypertension (a booking diastolic pressure of < 90 mm Hg, a maximum diastolic of 90 mm Hg and a diastolic increment of 25 mm Hg) Proteinuria (at least + protein in a random urine sample or 0.3 g in a 24-hour collection) Thrombocytopenia (platelet count of less than 100 109/L) Raised plasma alanine aminotransferase concentration ( 42 IU/L) or an increased plasma aspartate aminotransferase concentration ( 42 IU/L)
Eclampsia Eclampsia refers to the occurrence of one or more generalized convulsions and/or coma in the setting of pre-eclampsia and in the absence of other neurological conditions. The UK Obstetric Surveillance System (UKOSS) report gives an estimated incidence of 27.5 cases per 100,000 maternities with a case fatality rate estimated to be 3.1%. This was
OBSTETRICS
PEER REVIEWED
almost a halving of the incidence of eclampsia since 1992. Eclampsia remains to be associated with significant maternal morbidity, in particular cerebrovascular events (2.3%). The benefit of magnesium sulphate in the prevention of eclampsia has been well demonstrated, and magnesium sulphate has been shown to halve the risk of eclampsia among women with pre-eclampsia. Box 4 indicates the diagnostic criteria for eclampsia. Cerebral haemorrhage has been reported to be the most common cause of death in patients with eclampsia, and stroke is known to be the most common cause of death (45%) in women with HELLP syndrome.
Practice points
POSTPARTUM MANAGEMENT OF HYPERTENSION IN PREGNANCY

Blood pressure rises progressively over the first five postnatal days, peaking on days 36 after delivery. Research has focused on the antenatal complications, for both mother and baby, and the risks and benefits of administering antihypertensive therapy prior to delivery. There is very little information on how best to manage postpartum hypertension, regardless of type or severity, to optimize maternal safety and minimize hospital stay. Women with postpartum hypertension may also experience longer hospital stays and, possibly, heightened anxiety about their recovery. General NICE recommendations for postnatal care of women with hypertension in pregnancy include stopping methyldopa within 2 days of birth and asking the woman about severe headache and epigastric pain every time blood pressure is measured. In cases of mild or moderate pre-eclampsia platelet count, transaminases and serum creatinine should be measured 4872 hours after birth or step-down. These do not need to be repeated if results are normal. In most cases of gestational
Automated blood pressure devices may underestimate the blood pressure in pregnancy and therefore caution should be exercised in their use An appropriately sized blood pressure cuff should be used. If the mid-arm circumference is > 33 cm, a large cuff should be used Labetalol remains the antihypertensive of choice. Methyldopa and nifedipine may be used as second- or third-line agents Systolic blood pressures over 150 mm Hg should be treated Anaesthetists should anticipate an additional rise in blood pressure at intubation in women with severe pre-eclampsia who are undergoing caesarean section under general anaesthesia and take measures to avoid a speed that compromises maternal well-being, even when there are concerns about fetal well-being If the platelet count is < 20 109/L, a platelet transfusion is recommended prior to caesarean section or vaginal delivery Following delivery, the patient should be fluid restricted to 80 mL total fluid per hour until a natural dieresis occurs Ergometrine/oxytocin should not be given for the active management of the third stage if the mother is hypertensive or her blood pressure has not been checked Postpartum, women should be counselled appropriately regarding their risk of recurrence of pre-eclampsia as well as their increased risk of developing cardiovascular and renal disease
hypertension and pre-eclampsia, there is a rapid and complete resolution within 6 weeks of delivery of the fetus. Patients requiring antihypertensives can be weaned off slowly, and medications should not be stopped suddenly as there may often be a rebound hypertension.
Postnatal Follow-up All women who have had pre-eclampsia should be offered a medical review at the postnatal review (68 weeks) after the birth. Women who have had pre-eclampsia should be educated regarding their increased risk of development of cardiovascular disease, renal disease and cardiovascular risk facJPOG MAR/APR 2013 59
OBSTETRICS
PEER REVIEWED
tors for several years following pregnancy, and regular blood pressure checks with their general practitioner should be recommended. Women with severe pre-eclampsia have an increased risk of recurrence in their next pregnancy (about 1 in 6 [16%] pregnancies) but the disorder is generally less severe and manifests 23 weeks later than in the first pregnancy. This risk increases to about 1 in 4 (25%) pregnancies if the pre-eclampsia was complicated by severe pre-eclampsia, HELLP syndrome or eclampsia and led to birth before 34 weeks. The risk of recurrence is about 1 in 2 (55%) pregnancies if the pre-eclampsia led to birth before 28 weeks gestation. Women with essential hypertension should be encouraged to present for pre-conceptual counselling as antihypertensive medications such as ACE inhibitors are contraindicated in pregnancy and should be changed pre-conceptually. The use of low-dose aspirin in women with chronic hypertension moderately reduces the risk of developing superimposed pre-eclampsia, intrauterine growth retardation and perinatal death, and should be offered to all women at an early booking visit. The findings from the CLASP trial do not support routine treatment with aspirin of all women at risk of preeclampsia.
FURTHER READING
Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2007(1):CD002252. Centre for Maternal and Child Enquiries (CMACE). Saving mothers lives: reviewing maternal deaths to make motherhood safer: 200608. The eighth report on confidential enquiries into maternal deaths in the United Kingdom. BJOG 2011;118(suppl 1):1203. Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol 1988;158:892898. Hypertension in pregnancy. The management of hypertensive disorders during pregnancy. National Institute for Health andClinicalExcellence,www.nice.org.uk/guidance/CG107; August 2010. Knight M, Kurinczuk J, Spark P, Brocklehurst P. United Kingdom Obstetric Surveillance System (UKOSS) annual report. Oxford: National Perinatal Epidemiology Unit; 2007. Knight M. Eclampsia in the United Kingdom 2005. BJOG 2007;114:10721078. Koopmans CM, Bijlenga D, Groen H, et al. HYPITAT study group. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet 2009;374:979988. Milne F, Redman C, Walker J, et al. The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre-eclampsia in the community. BMJ 2005;330:576580. Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Lancet 2001;357:20022006. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Preeclampsia. Lancet 2010;376:631644. von Dadelszen P, Payne B, Li J, et al. PIERS Study Group. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet 2011;377:219227.
CONCLUSION
Hypertensive disorders are one of the commonest complications of pregnancy and may be associated with significant maternal and fetal morbidity and mortality. Although the aetiology of these disorders is becoming increasingly better understood, interventions to prevent hypertensive disorders of pregnancy have had poor results. The mainstay of treatment remains the use of antihypertensive medications, the use of magnesium sulphate in the prevention of eclampsia, and multidisciplinary input to ensure a timely delivery.
2012 Elsevier Ltd. Initially published in Obstetrics, Gynaecology and Reproductive Medicine 2012;22(6):141147.
About the Authors

Fergus P McCarthy is Specialist Registrar in obstetrics and gynaecology and Post Doctoral Research Fellow at The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland. Louise C Kenny is Professor of Obstetrics and Consultant Obstetrician and Gynaecologist, The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland.
PA PAEDIA EDIATRICS TRICS
II
Imaging Paediatric Brain Tumours Evaluation of the Acute Abdomen

Erica Makin, MBChB, MSc, FRCS (Paeds); Mark Davenport, ChM, FRCS (Eng), FRCS (Paeds)
Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology
INTRODUCTION
There is a multiplicity of causes of acute abdominal pain during childhood although for the purposes of this article those presenting predominantly during the neonatal period will be excluded. Although common sense tells us that most children with acute abdominal pain will have self-limiting conditions, it is important to identify those where there is a more serious surgical or medical emergency. The history of the complaint is the beginning of the diagnostic process and certain conditions are much more common in a particular age group, eg, intussusception. Still, accurate diagnosis can be challenging in the young non-verbal child or those with learning difficulties.
HISTORY AND SYMPTOMS

The timeline of symptoms should be ascertained with particular attention to onset, progression, location and the characteristics of other associated features, eg, fever, vomiting, stooling (constipation, diarrhoea), urinary symptoms, and gynaecological history in pubertal girls. History of accidental/non-accidental trauma, previous surgery or existing medical conditions should be ascertained. If a child is old enough to localize pain, this can be particularly helpful. In the younger child, parents may infer abdominal pain from the drawing up of legs, irritability, and inconsolability. Figure 1 shows possible surgical causes of abdominal pain based upon situation and lateralization, while Figure 2 illustrates a spectrum of causes by typical age group affected. Table 1 illustrates diagnosis by the characteristics of the vomit.
PAEDIATRIC S PAEDIATRICS
PEER REVIEWED
Figure 1. Diagnosis of abdominal pain in relation to location.
uncertain at presentation, although shift patterns in hospital conspire against this. Rectal examination in children has to be reserved for specific situations where the procedure is potentially life-saving (eg, rectal decompression in the enterocolitis of Hirschsprungs disease) or when the information gained is likely to be specific (eg, faecal impaction in those with idiopathic constipation). There is generally no role for rectal examination in the trauma setting, and if there are genuine concerns over a potential perineal/perianal injury then an examination under anaesthetic is more appropriate.
PERITONITIS
Peritonitis, the definitive sign of an acute abdomen, can be localized or generalized and usually occurs secondary to spreading microbial sepsis or soiling following perforation of a hollow viscus. The physical sign of peritoneal involvement is muscle guarding that is a reflex contraction of the abdominal wall muscles initially voluntary because probing hurts and then involuntary with onset of muscular rigidity. Peritoneal afferent nerve fibres become hypersensitive with inflammation, and palpatory tests such as percussion or rebound
PHYSICAL EXAMINATION
A thorough examination should be undertaken preferably when the child is comfortable. Appropriate analgesia should be given, although in the past this practice has been controversial. It was felt that provision of opiate analgesia may mask clinical findings and potentially cause a delay in making an accurate diagnosis. Randomized controlled trials in children have shown that administration of effective analgesia (intravenous opiates) does not delay in making an accurate diagnosis of appendicitis for instance. Repeated examination by the same physician is beneficial when the diagnosis is
are designed to detect this. As rigidity supervenes, breathing becomes painful and rapid to avoid peritoneal irritation. The phenomenon is largely clinical, and ancillary aids such as X-ray are merely confirmatory. Pneumoperitoneum may be detectable but be conscious of where the air might be risen to on a plain abdominal film. Maximize the chance of finding it using erect positioning or a shoot-through lateral film in the supine abdomen. Occasionally, children with ascites due to end-stage liver disease, nephrotic syndrome or on peritoneal dialysis may get spontaneous bacterial peritonitis and lack a septic focus. The commonest pathogens are Streptococcus pneumonia and E coli.
PA EDIA TRICS
PA ED IATRICS PEER REVIEWED
Figure 2. Causes of abdominal pain during childhood by age.
112 months Infantile colic Intussusception
15 years
612 years Non-specific abdominal pain Appendicitis
1318 years
Mesenteric adenitis (viral-associated abdominal pain) Gastritis/gastroenteritis
Incarcerated hernias (inguinal, rarely umbilical)

Hirschsprungs
Constipation Pharyngitis/tonsillitis
Internal hernias Cholecystitis/pancreatitis Crohns disease/ulcerative colitis
Metabolic diseases Midgut volvulus
Omental torsion, Meckels diverticulum Urinary tract infections

Urinary calculi
Ovarian torsion Pelvic inflammatory disease
Notes: Surgical, Non-surgical, Common, uncommon.
Diagnosis is confirmed by aspiration and microscopy, looking for presence of bacteria or a neutrophil count more than 250/mm3. Table 1. Differential diagnosis related to characteristics of vomit with abdominal pain
COMMON CAUSES OF ACUTE ABDOMINAL PAIN

Appendicitis Appendicitis was only really recognized as a distinct entity in the 1880s, followed by a huge increase in prevalence over the period of the 20th century. Over the past 20 years or so, there is some evidence that this surge has now come to an end and is now receding. This dramatic epidemiological variation has been attributed to the wider populations better access to clean water, better sewage disposal and the decline of all-pervading spectre of infantile gastroenteritis another manifestation of the so-called hygiene hypothesis. This has had the result of deferring exposure to pathogens later in life with possibly rapid lymphoid hyperplasia lead-
Vomitus Bilious (green)a
Differential diagnosis Intestinal obstruction Malrotation/volvulus Sepsis Gastritis Oesophagitis Gastric ulcer Oesophagitis Gastritis Gastric/duodenal ulcer Mallory-Weiss tear Gastroenteritis Early intestinal obstruction Late intestinal obstruction
Coffee grounds
Fresh blood
Food/stomach contents Faeculent

a
Bile is golden yellow as it is secreted into the duodenum, becoming green when exposed to stomach acid.
PEER REVIEWED
It is challenging to diagnose with accuracy the causes of acute abdominal pain in the young child.
ing to luminal occlusion in the base of the appendix triggering appendicitis. Appendicitis is the commonest acute surgical emergency and overall accounts for over 40,000 admissions in the UK every year. It is commonest in those aged 1020 years and slightly more prevalent in boys. It is commonly quoted that the lifetime risk for the development of appendicitis is about 7%. It is also increasingly recognized that there may be two distinct strands of appendicitis; one with rapid and early progression to perforation and perhaps gangrene and the other more indolent and slowburning.
cific abdominal pain. Palpation of a tender mass in the RLQ is indicative of a so-called appendix mass which is simply an appendicitis enveloped by omentum and surrounding bowel loops. In the younger child of less than 5 years, possibly due to the absence of omentum, the perforation and complication rate is high and has been reported up to 70%. While no symptom or sign is invariable in every case, when enough are present then little more is required to make the diagnosis. There are however two problematic positions of the appendix and one problem age group where diagnosis is not straightforward. Pelvic appendicitis (20%) is almost always misdiagnosed initially, as there is no RLQ pain or tenderness and there are often contrary features. The symptoms are usually supra-pubic and with increasing peritonitis in the pelvic pouch, involvement of the bladder causing dysuria, and the rectum causing feelings of incomplete but painful defaecation (tenesmus) of loose stool. Urine tests may well be falsely positive, and most have been partly treated with antibiotic as a urinary tract infection or gastroenteritis.
Clinical Features The classical features are of visceral poorly localized periumbilical pain shifting to the right lower quadrant (RLQ) and becoming parietal in character with localization of tenderness, cough, and movement exacerbation. Mild fever, limited vomiting and anorexia complete the picture. The length of history is important, specifically in those with pain greater than 48-hour duration, then it is either likely to be complicated appendicitis or alternatively non-speJPOG MAR/APR 2013 64
PA EDIA TRICS
Table 2. Paediatric Appendicitis Score (PAS) and Alvarado score Paediatric Appendicitis Score Variable Pain migrating to RLQ Anorexia Nausea/vomiting Fever >38C RIF tenderness Pain with cough/percussion/hopping WBC > 10,000 cells/mL Neutrophils > 7,500 cells/mL Total score Score 1 1 1 1 2 2 1 1 10 Variable Pain migrating to RLQ Anorexia Nausea/vomiting Fever >37.3C RIF tenderness Rebound tenderness WBC > 10,000 cells/mL Raised neutrophils Total score Alvarado Score Score 1 1 1 1 2 1 2 1 10
Notes: RIF right iliac fossa; RLQ right lower quadrant; WBC white blood cell count.
Retrocaecal or retrocolic appendicitis (20%) is misdiagnosed because the local signs are masked by the overlying bowel and the separation of the site of retroperitoneal inflammation from the peritoneal cavity. The appendix tip may well be much higher, leading to tenderness being in the right upper quadrant rather than the RLQ and because of the delay will have often formed a collection or abscess by the time of admission. Extending the hip may exacerbate pain due to involvement of the iliopsoas muscle, and these children often lie on the bed with their hip flexed. The teenage girl has many possible causes for right iliac fossa (RIF) pain that are not only gynaecological (eg, pelvic inflammatory disease, ovarian torsion, mittelschmerz pain, and even pregnancy, ectopic or otherwise) or urological but also related to more functional intestinal problems such as irritable bowel. This group has the highest white appendicectomy rate among large surgical series of appendicectomies testifying to the diagnostic difficulties. All such girls should have urine tested for infection (dipstick for nitrites and leucocytes, and microscopy for cells) and exclusion of pregnancy
(-human chorionic gonadotropin test) and there should be a low threshold for pelvic ultrasound before committing to theatre even in the obvious case of appendicitis.
Investigations The simplest are used to reflect inflammation and infection and include a white blood cell and specifically neutrophil count and the acute-phase C-reactive protein. The latter may rise within 24 hours of insult and has a short half-life of 18 hours in the circulation. Levels of more than 10 mg/L are considered abnormal and suggestive of pathology. However, neither test is specific to appendicitis, and perhaps they have more value in longer-duration pain where one might expect a change to have occurred and conversely if resolutely normal confirming an impression of non-specific abdominal pain. In case of diagnostic doubt and teenage girls an ultrasound scan should be the next step. It is non-invasive and widely available; but it is userdependent and reported accuracy varies with sensitivities of 74100% and specificities of 8899%. Visualizing a tender thick-walled tubular structure
PEER REVIEWED
The differential diagnosis for right iliac fossa pain in the teenaged girl includes gynaecological, urological and intestinal causes.
eg, Crohns disease, ulcerative colitis and, even in children, abdominal neoplasms such as lymphoma and carcinoid tumours. Measures such as focused CT (limited to lower abdomen) may improve acceptability and reduce the radiation exposure. One approach, which does seem to focus the mind of the clinician, is the use of clinical scoring tools, of which there are two currently in use (Table 2). These are the Paediatric Appendicitis Score (PAS) and the Alvarado score. Both virtually overlap in terms of the items assessed, and each requires a blood test although there are slight differences in thresholds and weighting. Using PAS, 2 suggests not-appendicitis the extreme scores and discharge home while 7 is consistent with appendicitis and advises operation. In a large study from Vancouver, Canada, the use of a PAS score was tested in 849 children with suspected appendicitis. Using the thresholds mentioned, three children would have been sent home with appendicitis whereas 29 would have had normal appendices removed from the 123 (24%) children who had appendicectomy. The concept of active observation was en-
in the RIF is ideal but can be difficult in obesity or when the appendix is unusually sited. Other more nebulous signs may be seen such as hyperechoic mesenteric fat, free fluid in the RIF, localized and dilated small bowel loops, and even a calcified faecalith. Computed tomographic (CT) scans with contrast (oral/rectal) have possibly the highest overall sensitivity (94%) and specificity (95%) in diagnosing appendicitis but are much more often used in adults with suspected appendicitis than in children. The hazards of ionizing radiation are clear. A single abdominal CT scan in a 5-year-old gives estimated lifetime excess risk of radiation-induced cancer of 26 per 100,000. CT is much better at arriving at alternative diagnoses masquerading as appendicitis,
couraged by Peter Jones, a surgeon from Aberdeen, and this implied admission of children with suspected appendicitis and repeated clinical examination (by the same examiner). Those with appendicitis would then declare themselves after 1224 hours and the rest would get better. While admirable, in this shift-driven era and conscious of the European Working Time Directive, such continuity may be difficult to achieve. Laparoscopy as a diagnostic tool is becoming the definitive investigation for persisting undiagnosed RLQ pain, following a non-diagnostic ultrasonography in children. This should resolve doubt and provide an alternative explanation for most pain. In those where the appendix looks normal, then the consensus is to remove it.
PA EDIA TRICS
Surgery of Appendicitis Appendicectomy remains the surgical therapy of choice although there have been some studies in adults looking at the value of antibiotic-only regimens for uncomplicated appendicitis. These have tended to show absence of real benefit and a tendency to recurrence even if the first episode was successfully treated. Surgery should be performed expeditiously but seldom as an emergency and be preceded by a period of appropriate fluid resuscitation and adjuvant antibiotics effective against gram-negative and anaerobic organisms as the likeliest source of intra-peritoneal sepsis. Classically, a RIF muscle-splitting incision has been used, but appendicectomy can also be accomplished safely with either multiple or single laparoscopic ports. However performed, the hospital stay should be short and day-case surgery has even been reported in children. Those with complicated appendicitis (eg, perforation, peritonitis, gangrene) require a longer period of therapeutic antibiotics and should be monitored assiduously for problems and complication such as surgical site infection.
Appendicitis is a common surgical cause of acute abdominal pain in children.
INTUSSUSCEPTION
Intussusception is a life-threatening surgical emergency, most commonly occurring between 3 months and 2 years of age. It occurs when a segment of bowel (the intussusceptum) invaginates into the distal bowel (the intussuscipiens). This results in initially venous and lymphatic congestion, bowel obstruction, and eventually necrosis and perforation. Any part of the intestine can become intussuscepted, but it most commonly affects the terminal ileum into the ascending colon. The initiating aetiological factor in most cases is a pathological lead point such as a polyp, although in some instances of post-operative intussusception this appears difficult to define.
Almost 90% of cases are described as idiopathic and occur in the typical age group. It is suggested that in this population, there is a normal if profound hyperplastic change occurring in distal ileal lymphoid tissue due to weaning, exposure to gastrointestinal viruses, and pathogens, etc, which acts as a lead point. There is therefore some evidence to implicate viruses such as adenovirus, rotavirus, human herpesvirus 6, etc, together with other causes of bacterial enteritis such as Salmonella spp, Escherichia coli, Shigella and Campylobacter. Therefore, even if a child presents with recurrent severe abdominal pain and diarrhoea with a positive stool culture, it can be important to exclude an intussusception if the symptoms do not resolve. In the remaining cases, a pathological lead
PEER REVIEWED
Gastroenteritis is a common non-surgical cause of acute abdominal pain in children.
Clinical Features Typically, this is of a young child with a recent viral illness who presents with vomiting and intermittent colicky abdominal pain manifest as inconsolable crying. Diarrhoea may be reported in about a third, and passage of altered blood and mucus is a characteristic red currant jelly stool. On abdominal examination between the episodes of pain the child is often lethargic, and an abdominal mass should be sought either in the right upper quadrant or the epigastrium the RIF having a characteristic emptiness (Dances sign). Unfortunately, many of these symptoms are non-specific, and the condition can go unrecognized until quite late with the child becoming progressively shocked. Investigations Abdominal X-ray is a reasonable option and may show a paucity of gas in the RIF, distended loops of small bowel due to the obstruction, and a softtissue mass. There are two specific signs: the target sign which appears as two concentric circles superimposed over the right kidney shadow caused by peritoneal fat surrounding and within the intussusception, and the crescent sign where there is a soft-tissue mass projecting into bowel gas. Less commonly, there may be free air in the peritoneal cavity indicative of perforation. However, the preferred diagnostic modality is abdominal ultrasound, which has a sensitivity and specificity of more than 95% and may also show the target sign or the pseudo-kidney sign as it appears in longitudinal section. Management These children require intravenous fluid resuscitation as they are prone to dehydration secondary to prolonged vomiting and small bowel obstruction. Antibiotics should also be given because of the ischaemic bowel and tendency to bacterial translo-
point can be identified, and underlying causes have included Meckels diverticulum, jejunal-ileal polyposis (eg, PeutzJeghers syndrome), mesenteric lymphadenopathy, lymphoma, HenochSchonlein purpura (where there is a sub-mucosal haematoma acting as lead point), cystic fibrosis, and appendiceal stump. Sometimes, a jejunojejunal or ileo-ileal intussusception occurs in the early post-abdominal surgery period and is presumably related to disorder restoration of intestinal motility. These can be especially hard to diagnose particularly as they can resolve spontaneously.
PA EDIA TRICS
cation. If the child is haemodynamically stable and there are no signs of bowel perforation (on examination or abdominal X-ray), then a non-operative reduction can be attempted. Air enema reduction has superseded the original barium enema technique, but reported success rates can vary between 50% and 80%. Certainly pneumatic reduction appears safe, and pressures can be monitored more accurately than before. A maximum pressure of about 120 mm Hg can be used, and the reduction is done under fluoroscopic screening. A successful reduction is confirmed when there is free flow of air into the terminal ileum. If there is doubt, then a repeat ultrasound can be performed to confirm complete reduction. If it is initially unsuccessful, the procedure can be repeated assuming the child remains stable.
is less clear now, and each case should be judged on its own features. A conventional open approach involved a right-sided transverse incision where the mass can be delivered into the wound and the intussusceptum pushed out. The bowel should be examined carefully and, if there is an obvious cause (eg, Meckels diverticulum), dealt with appropriately. Resection may also be needed if there has been necrosis. Laparoscopic reduction can be done, but actual manipulation and reduction can be much more difficult using instruments. Recurrence may occur in up to 15% of air contrast reductions and 5% of operative reductions and be an early or late phenomenon. Certainly if it keeps on happening, there must be strong suspicion of a pathological lead point. Some authors also suggest the use of glucocorticoids to treat recurrence in the idiopathic group because of the putative relationship to lymphoid hyperplasia.
Unfortunately, many of these symptoms are non-specific, and [intussusception] can go unrecognized until quite late with the child becoming progressively shocked
MIDGUT MALROTATION AND VOLVULUS

Malrotation is the intestinal feature which in itself may be completely without symptoms, but volvulus is the complication and can be catastrophic. The primary symptom is bilious vomiting and is indicative of duodenal obstruction and should never be disregarded. Although rotational anomalies of the intestine are probably common and estimated to occur between 1 in 200 live births, the frequency with which it becomes symptomatic is much less common, possibly 1 in 6,000 live births. Typically, it presents
Surgery is indicated when air enema reduction has failed or in cases where there is obvious pneumoperitoneum or the signs strongly suggest necrotic bowel. Formerly, the time from onset of symptoms was regarded as an important indicator as to contrast enema reduction or surgery although this
within the first year of life but can present at any age even into adulthood.
Embryology of the Midgut There are three distinct stages. From the 5th to 10th week, there is rotation of the duodeno-jejuJPOG MAR/APR 2013 69
PEER REVIEWED
Research has shown that use of opiate analgesia does not interfere with the diagnosis of acute surgical causes of abdominal pain in the child.
nal (DJ) flexure anticlockwise behind the superior mesenteric axis (artery [SMA] and vein [SMV] axis) to lie in the left upper quadrant. Then from about the 10th week, there is a 270 rotation of caecocolic loop from left lower quadrant coming to lie in front of the DJ flexure. Finally, from the 11th week onwards, the anticlockwise rotation of the caecocolic pole continues bringing it to the RLQ. Retroperitoneal fixation occurs to the duodenum and the ascending and descending colon. The two ends of the small bowel should therefore be fixed and lie in opposite quadrants. Non-rotation refers to failure of the whole process, with malrotation referring to various degrees of failure to complete the process. The commonest variant is where the final 90 does not happen with the caecum in the right upper quadrant
or epigastrium overlying the duodenum and bringing together the DJ flexure and caecum. There is now a pronounced bottle neck to the small bowel, making volvulus that much easier. Should it occur, the lumen of the duodenum and mesenteric vessels become compromised, and if complete duodenal obstruction occurs then potentially catastrophic venous infarction may follow. The situation of the caecum overlying the duodenum itself may cause external duodenal compression, attributed to the so-called Ladds peritoneal bands, but obviously without any vascular compromise.
Clinical Features Over 80% will present within the first week of life, and all symptomatic cases will present with signs of duodenal obstruction and therefore bilious vom-
PA EDIA TRICS
iting. When there is bowel ischaemia and potentially infarction due to volvulus, the abdomen should be tender with signs of peritonism. There may be evidence of gastrointestinal haemorrhage from either end, resulting in circulatory collapse and shock due to blood loss and fluid sequestration with endotoxaemia and sepsis. Malrotation may have a more chronic course with intermittent bilious vomiting. Cases have been described where volvulus has happened without actual infarction but leading to small bowel oedema and protracted symptoms of failure to thrive, malabsorption and food intolerance, protein losing enteropathy, and chylous ascites. Malrotation may be associated with other conditions such as gastroschisis, exomphalos, diaphragmatic hernias, duodenal atresia, jejunal atresia, biliary atresia, various heterotaxy syndromes, and trisomy 21.
volvulus is suggested if there is absence of passage of contrast from the duodenum or a corkscrew or spiral orientation of the proximal jejunum. The false-negative rate is 614% and the false-positive rate is 715%. If there is doubt over the diagnosis, a delayed plain abdominal X-ray may be useful to assess the position of the caecum. Abdominal ultrasound is of no use for determination of bowel orientation but may be used to try and determine the orientation of the SMA and SMV with the former normally located to the left of the latter. The so-called whirlpool sign suggests volvulus.
Investigations In an infant presenting with an acute abdomen, bilious vomiting and shock then every minute counts and sometimes there is no time for diagnostic imaging, beyond perhaps an abdominal X-ray. Although this is rarely specific, its very featureless and gasless appearance supports the diagnosis. Urgent fluid resuscitation and laparotomy are indicated and should be performed without delay in an attempt to save any viable bowel. Still, mortality is high and the morbidity of short bowel is significant. However, if the child is stable, the key diagnostic modality is an upper gastrointestinal contrast study (barium or water soluble) to assess the position of the DJ flexure. Typically, the normal position is defined as the DJ flexure should lie to the left of the left pedicle and in the transpyloric plane. Initial proximal jejunal loops should then be on the left of the abdomen. Malrotation is suggested by abnormal positioning of the DJ flexure;
Management The principles of surgical management are to untwist a volvulus and save as much bowel as possible. Frankly, necrotic bowel should be resected, but borderline segments may be left to a second-look laparotomy at 3648 hours. The classical treatment of malrotation is to widen the mesentery and separate the ends of the small bowel as far apart as possible. This is best accomplished by replicating the original non-rotated state with the duodenum and small bowel on the right and the large bowel on the left the Ladds procedure.
INTRA-ABDOMINAL: MEDICAL AND UNUSUAL CAUSES

(i) Acute bacterial and viral gastroenteritis is clearly very common, but the pain, if any, should be colicky and associated with vomiting and diarrhoea. Family members and foreign travel may be involved. There should be no peritonism. Haemolytic ureamic syndrome, seen typically in toddlers, may be an extreme example of verotoxin producing E coli sepsis. (ii) Foregut inflammation (eg, gastritis, oesophagitis, duodenal ulceration) may be reJPOG MAR/APR 2013 71
PEER REVIEWED
Learning objectives
EXTRA-ABDOMINAL AND SYSTEMIC CAUSES

Abdominal pain may be a symptom of a disease process/condition in an adjacent region or as part of a systemic illness. (i) Lower lobe pneumonia caused by inflammatory pleuritic involvement of the diaphragm and lower chest wall. (ii) Pharyngitis and tonsillitis particularly that caused by group A beta-haemolytic streptococci. (iii) Sickle cell disease (SCD) and abdominal crisis gene mutation causing single aminolated to ingestion of toxins in food, acid or alkali, various chemicals, H pylori colonization, etc. Most are self-limiting, but upper gastrointestinal endoscopy may have a role. (iii) Inflammatory bowel disease much more likely to pursue a chronic course, but toxic megacolon can be the presenting feature of ulcerative colitis and acute small bowel obstruction or a masquerade of appendicitis in ileal Crohns disease. (iv) Gallstones and cholecystitis found in association with adolescent, overweight females and SCA. Choledochal malformation is rare and usually has a chronic history. Ultrasound is the key investigation. (v) Pancreatitis in this age group can be related to trauma (often trivial), gallstones, drugs malformation. Serum amylase is sensitive and (relatively) specific. (vi) Urosepsis commonly found in both boys and girls in pre-school age group and in adolescent girls. Symptoms more specific for the latter group. Pyelonephritis, etc, should lateralize, but features can be notoriously non-specific. Urine dipstick, microscopy and culture are key. acid substitution in the -globin gene (usually HbSS, but also HbSC) and leading to abnormally rigid red cells prone to sickling. Common in those of Afro-Caribbean origin, West Africa being the epicentre of the disease, but is sometimes found in eastern Mediterranean countries and India. Is seldom silent when homozygous and detectable on newborn screening. Vaso-occlusion in mesenteric or solid organ capillary beds leads to severe recurrent abdominal pain. Treated conservatively with rehydration, oxygenation, and blood transfusion. Genuine intra-abdominal pathology is also more common in sickle cell disease gallstones, splenic sequestration, and infarction. Appendicitis is said, however, to be less common in SCD. matory condition affecting lining membranes such as the peritoneum, tunica vaginalis, pericardium, etc, and caused by single gene mutation (AR) which leads to a defect in the protein pyrin. The gene is present in Eastern Mediterranean populations (eg, Turkey, Lebanon, Armenia). May present as abdominal pain due to peritonitis in older children, with a rash seen
After reading this article, you should be able to: understand the principal causes of the acute abdomen in infants and children develop a structured approach to the assessment of the abdomen in order to reach a differential diagnosis utilize investigative modalities appropriately, eg, laboratory tests, radiology distinguish between medical and acute surgical causes of abdominal pain understand the management of common causes of abdominal pain
(eg, valproate, chemotherapy) and choledochal (iv) Familial Mediterranean fever autoinflam-
PA EDIA TRICS
in about 20%. C-reactive protein is invariably high, and colchicine is a specific treatment. (v) HenochSchonlein purpura (HSP) a systemic vasculitis caused by IgA immune complex deposition in various capillary beds. The trigger or cause of HSP, though, is unknown but may follow an upper respiratory infection. It occurs more in boys and most are under 6 years of age. The rash is predominantly purpuric (purple and 310 mm in diameter), nonblanching and occurs largely over the legs and buttocks. Central, colicky abdominal pain is a feature in about 60% and may precede the rash. Joint pain is also common and should be sought. Gastrointestinal bleeding may occur and be due to actual intussusception. Palpate for a mass and obtain early ultrasound in atypical cases. (vi) Mycobacterium tuberculosis fortunately this is now a rare cause of chronic bacterial peritonitis but should be considered in children with a positive family history, recent travel to endemic countries, those who have not been vaccinated, and the immunocompromised. (vii) Diabetic ketoacidosis severe abdominal pain may be the presenting feature for usually adolescents with type 1 diabetes. There may be vomiting and diarrhoea adding to the invariably severe dehydration. Specific clues are the air hunger Kussmaul-type breathing pattern and ketotic smell. Whatever the abdomen feels like, such patients need intensive rehydration, correction of their electrolyte and glucose imbalance before making a surgical commitment. (viii) Testicular torsion abdominal or groin pain may be the only volunteered symptom from a shy teenage boy. Testicular examination should be part of a routine abdominal examination.
FURTHER READING
Alloo J, Gerstle T, Shilyansky J, Ein SH. Appendicitis in children less than 3 years of age: a 28-year review. Pediatr Surg Int 2004;19:777779. Bailey B, Bergeron S, Gravel J, Bussires JF, Bensoussan A. Efficacy and impact of intravenous morphine before surgical consultation in children with right lower quadrant pain suggestive of appendicitis: a randomized controlled trial. Ann Emerg Med 2007;50:371378. Becker T, Kharbanda A, Bachur R. Atypical clinical features of pediatric appendicitis. Acad Emerg Med 2007;14:124129. Bhatt M, Joseph L, Ducharme FM, Dougherty G, McGillivray D. Prospective validation of the pediatric appendicitis score in a Canadian pediatric emergency department. Acad Emerg Med 2009;16:591596. Choong CK, Beasley SW. Intra-abdominal manifestations of HenochSchnlein purpura. J Paediatr Child Health 1998;34:405409. Doria AS, Moineddin R, Kellenberger CJ, et al. US or CT for diagnosis of appendicitis in children in adults? A metaanalysis. Radiology 2006;241:8394. Goldman RD, Carter S, Stephens D, Antoon R, Mounstephen W, Langer JC. Prospective validation of the pediatric appendicitis score. J Pediatr 2008;153:278282. Green R, Bulloch B, Kabani A, Hancock BJ, Tenenbein M. Early analgesia for children with acute abdominal pain. Pediatrics 2005;116:978983. Laje P, Martnez-Ferro M. Acute abdomen. In: Sinha C, Davenport M, eds. Handbook of pediatric surgery. London: Springer; 2010:173176. Samuel M. Pediatric appendicitis score. J Pediatr Surg 2002;37:877881. Shew B. Surgical concerns in malrotation and midgut volvulus. Pediatr Radiol 2009;39(suppl 2):S162 S171. Shlamovitz GZ, Mower WR, Bergman J, et al. Lack of evidence to support routine digital rectal examination in pediatric trauma patients. Pediatr Emerg Care 2007;23:537543. Waseem M, Kotlus Rosenberg H. Intussusception. Pediatr Emerg Care 2008;24:793800. Williams H. Green for danger! Intestinal malrotation and volvulus. Arch Dis Child Educ Pract Ed 2007;92:ep8791.
2012 Elsevier Ltd. Initially published in Paediatrics and Child Health 2012;22(6):217223.
About the Authors

Erica Makin is a Specialist Registrar in Paediatric Surgery in the Department of Paediatric Surgery, Kings College Hospital, London, UK. Mark Davenport is Consultant Paediatric Surgeon in the Department of Paediatric Surgery, Kings College Hospital, London, UK.
GYNAECOLOGY GYNAECOLOGY PAEDIATRICS PAEDIATRICS
II
The Management Imaging Paediatric of Perimenopausal Bacterial BrainVaginosis Tumours Menstrual Symptoms
Phillip Hay, MBBS, FRCP Tang Phua Hwee, MBBS, FRCR, MMed Diagnostic Radiology John Eden, MB BS, MD, FRCOG, FRANZCOG, CREI; Sheila ONeill, MB BCh, BAO, PhD, FRACGP
INTRODUCTION
The forties are often a time of hormonal turbulence in a womans life. Fluctuating sexhormone levels and anovulatory cycles can affect the brain causing flushes, sweats and mood swings, the breasts causing swelling and pain, and the uterus causing abnormal uterine bleeding (AUB). It is this latter dilemma, namely AUB, that is the focus of this article. For this paper, the search engine Sirius was used via the University of New South Wales Library website using the keywords perimenopause, abnormal uterine bleeding, investigation, terminology, management, fibroid, adenomyosis, polyp, endometrial hyperplasia, endometrial cancer, hormone replacement, levonorgestrel intrauterine device, endometrial ablation, hysterectomy, contraceptive pill, progestin, and tranexamic acid. Preference was given to reviews, especially meta-analyses and systematic reviews. Perimenopause is defined as the time of menstrual irregularity leading up to the last period (menopause) and the 12 months following the last period. The Stages of Reproductive Ageing Workshop (STRAW) suggested the term menopause transition leading up to the last menstrual period and divided this phase into two parts. Stage 0 is menopause (last period). Stage 2 (early menopause transition) is characterized by more than 7 days of cycle variation compared with normal and stage 1 (late menopause transition) as greater than two skipped cycles with at least 60 days of amenorrhoea. Pelvic pathology is also commonly found in this age group. As such, some women will need to be investigated to exclude (pre-) malignancy and to help decision making about the best treatment option. A Fdration Internationale de Gyncologie et dObsttrique (FIGO) working group has classified AUB into nine categories Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia, Coagulopathy, Ovulatory disorders, Endometrium, Iatrogenic, and Not Classified (acronym: PALM-COEIN).
G YNA ECOLOGY
YNA ECOLOGY I GPEER REVIEWED
The levonorgestrel-releasing intrauterine system is the most effective option for menstrual control in perimenopausal women.
Leiomyoma (L) are further subclassified into those who have at least one sub-mucus fibroid (Lsm) and those with fibroids which do not impact on the endometrial cavity (Lo). Endometrial hyperplasia and malignancy and occasionally cervical cancer can present with AUB. The Coagulopathy group includes conditions such as von Willebrand disease, although this usually declares itself in the teenage years and is often associated with abnormal bleeding after childbirth, dental work or surgery, gum bleeding, bruising, and epistaxis. Endometrial causes suggest a primary problem in the endometrium, and as research in this area progresses, it is likely that specific biochemical and/ or genetic problems will be defined. The Iatrogenic group includes breakthrough bleeding on hormone preparations such as the oral contraceptive pill (OCP), hormone therapy (HT), and levonorgestrelreleasing intrauterine systems (LG-IUS). There is a lack of consensus of definitions and
terminology of AUB and outcome measures (Confino 2007). Until recently, there has been an abundance of old descriptive terms for AUB which have not been helpful.
WHEN TO INVESTIGATE
A concise history and examination need to be performed first. Large fibroids may present with the woman noticing a pelvic mass or bladder frequency, but most will be concerned about a change in their menstrual pattern. Menstrual history should focus on frequency, cycle regularity, duration, and heaviness of flow. Frequent, heavy and/or prolonged bleeding usually requires some investigations as does postmenopausal bleeding. Physical examination may reveal a polyp, a fibroid uterus, or some other lesion. Pallor may indicate anaemia. Laboratory tests may include a Papanicolaou smear, cervical cultures, full blood
GYNAECOLOGY
PEER REVIEWED
Table 1. Limitations of endometrial biopsy
INVESTIGATIONS
The guidelines of the American College of Obstetricians and Gynecologists mandate that all women over 35 years with AUB should have an endometrial assessment (ACOG Committee on Practice Bulletins 2001). The tests available will vary according to location but include TVUS, endometrial biopsy (EB), sonohysterogram (SHG; or saline infusion sonogram), dilation and curettage (D&C), and hysteroscopy. Historically, D&C was the mainstay of endometrial assessment. However, its main drawbacks include the need for a general anaesthetic, missed
Factors that might make it difficult to perform an endometrial biopsy: Cervical stenosis (cervical surgery, multiple caesarean sections) Pain Sharply anteverted or retroverted uterus Has the cavity been adequately sampled? Considerations: Uterine shape and size (eg, bicornuate uterus) Location of a lesion (eg, it is difficult to sample a cornual lesion) Size of lesion Is the lesion affecting most of the endometrium or localized?
count, iron studies, and occasionally tests for bleeding disorders. All women with AUB who are in the perimenopausal age range will need their uterus assessed because many will have structural anomalies and some premalignant and malignant conditions, the commonest being endometrial hyperplasia. Around 70% of women presenting with AUB will have a benign cause, 15% carcinoma, and 15% a premalignant condition. Management algorithms have been published, but in the end, if endometrial hyperplasia is suspected, then the endometrium will need to be assessed and most will require at least transvaginal pelvic ultrasound (TVUS). Risk factors for endometrial hyperplasia or cancer include obesity, age over 40 years, polycystic ovary syndrome, exposure to unopposed oestrogen therapy, tamoxifen usage, and postmenopausal bleeding. Many will present with AUB. It is not the intent of this review of perimenopausal menstrual symptoms to describe the management of endometrial hyperplasia; although it needs to be stated that any degree of atypia will usually necessitate hysterectomy because of the risk of small occult carcinoma being already present as well as the significant risk of progression to carcinoma.
pathology, or incomplete removal of an intra-cavity lesion, free floating tissue left in situ , and a high false-negative rate. Complications included uterine perforation and intrauterine adhesions.
EB COMBINED WITH TVUS

Office EB using the Pipelle device is a cost-effective tool for investigating AUB especially when combined with TVUS. Endometrial hyperplasia and carcinoma are unlikely if the endometrial thickness (ET) is 4 mm or less. This is very useful for assessing postmenopausal bleeding (later), but unfortunately many perimenopausal women will have thick ET because of unopposed oestrogen surges and so some form of tissue sampling is very helpful in this group (the National Institute for Clinical Excellence recommends EB in all cases of AUB, age > 40). The Pipelle device can provide a histological diagnosis of most endometrial pathologies with some limitations (Table 1). Typically, the Pipelle system is very good at detecting pathologies that involve most of the endometrial cavity but can miss small focal lesions, including cancers. In one study, Pipelle sampling was done prior to hysterectomy for known endometrial cancer. Over 95% of the sample were
G YNA ECOLOGY
adequate for histological examination, and the sensitivity for picking up the malignancy was 83%.
and failed or ineffective treatment, then an EB is indicated to exclude endometrial cancer or atypical hyperplasia.
HYSTEROSCOPY
Hysteroscopy allows the entire uterine cavity to be visualized, and any lesions found can be visualized and biopsied. This is can be performed in the office or in theatre. Hysteroscopy cannot assess the myometrium and so may miss adenomyosis and will not allow evaluation of the size and depth of fibroids.
The guidelines of the American College of Obstetricians and Gynecologists mandate that all women over 35 years with AUB should have an endometrial assessment
If a focal lesion is found on TVUS, then hysteroscopy can be used to visualize and biopsy the lesion. If a uterine anomaly such as a septum is found on TVUS, then a LG-IUS is likely to be expelled. Fibroids are common in this age group, and TVUS is accurate in detecting, measuring and locating them (with perhaps the exception of sub-mucus fibroids). These factors will be important in determining the likely success of treatment options such as LG-IUS, hormonal therapies, and endometrial ablation. If a fibroid uterus is found on examination or at TVUS, then a SHG can be helpful in assessing sub-mucus fibroids prior to attempting hysteroscopic resection. SHG can also detect most polyps.
SONOHYSTEROGRAM
Saline instilled into the uterine cavity permits ultrasound to visualize its contents. It is an accurate test and cheaper than hysteroscopy. If a lesion is found, then hysteroscopy and biopsy will be indicated. Meta-analyses have shown that SHG misses around 7% of lesions (usually a small endometrial polyp).
TVUS VERSUS HYSTEROSCOPY VERSUS SHG

Farquhar performed a systematic review of all three modalities and found that all three tests were moderately accurate in detecting intrauterine pathology. SHG and hysteroscopy were better than TVUS for detecting sub-mucus fibroids. Hysteroscopy is considered the 'gold standard' test to assess the endometrium, especially for endometrial hyperplasia and cancer. However, in clinical practice, each test has its place and can help both with diagnosis and selection of the best treatment option for the individual patient. For all patients with AUB, a TVUS will be the first test ordered, backed up with an EB. According to Royal College of Obstetricians and Gynaecologists guidelines, if there is persistent intermenstrual bleeding in a woman aged 40 years or above
POSTMENOPAUSAL BLEEDING
Bleeding after menopause always requires uterine assessment. Numerous trials and systematic reviews have shown that TVUS is a very good first test, and if the ET is 4 mm or less then significant endometrial pathology is unlikely. ET greater than 4 mm (5 mm or more) or repeated episodes of postmenopausal bleeding (even if the ET is 4 mm or less) is an indication for SHG or (usually) hysteroscopy.
GYNAECOLOGY
PEER REVIEWED
Table 2. Contraindications to the contraceptive pill
This can be achieved by either inserting the device just after menstruation or by pre-treatment with a progestin or contraceptive pill. In the long term, the LG-IUS reduces menstrual blood loss by over 90%. It works best in those with a normal uterus, although it can control a fibroid uterus, especially if there are no sub-mucus lesions, and if the uterus is not too large. There may be a higher expulsion rate if fibroids are present. If menopausal symptoms such as hot flushes are present, then concomitant oestrogen can be given as the LG-IUS will prevent endometrial hyperplasia. Systematic reviews have shown that the LG-IUS and endometrial ablation gave similar results for heavy menstrual loss if sub-mucus fibroids are not present.
History of venous or arterial thrombosis or other cardiovascular events Uncontrolled hypertension Advanced diabetes or liver disease Headaches with neurological manifestations Smokers older than 35 years of age Women with known or suspected breast, endometrial, vaginal or cervical cancer Undiagnosed abnormal vaginal bleeding Caution and additional counselling may be required: Family history of breast cancer Personal history of atypical breast lesion Migraine, diabetes, hyperlipidaemia (especially hypertriglyceridaemia) Depression (some progestins can aggravate depression) Gallbladder, liver, heart or kidney disease, hypertension
CONTRACEPTIVE PILLS
If there are no contraindications (Table 2), then a
TREATMENT OPTIONS
Non-steroidal anti-inflammatory drugs reduce menstrual blood loss by 25% on average, tranexamic acid by around 50%. The latter drug has also been shown to induce necrotic changes in fibroids. Many perimenopausal women will be troubled by irregular menstrual cycles, sometimes short, and other times long and variable flow. Thus, treatment goals are usually menstrual regulation, reduction of menstrual loss, and the prevention of endometrial hyperplasia. The next section will focus on the LGIUS, OCPs, sequential HT, and endometrial ablation.
low-dose OCP can control both the irregular cycle and the symptoms of the perimenopause. Longcycle regimens can be used to skip periods. There are scant data on the use of OCP in women over 50 years, although OCPs containing oestradiol, rather than ethinyl-oestradiol, are now available. Theoretically, these should be safer for perimenopausal women, although definitive data are not yet available.
PROGESTINS AND SEQUENTIAL HT

Progestins have anti-oestrogenic, anti-proliferative and atrophying effects on the endometrium. Their impact depends upon the type, dose and regimen used. These can be given alone or in combination with oestrogens as in the OCP or HT. Continuous progestins, in adequate dosage, can completely suppress menstruation (eg, depot injection of medroxyprogesterone acetate), but most commonly progestins are given cyclically. Ten days of luteal
LEVONORGESTREL-CONTAINING INTRAUTERINE SYSTEM

The LG-IUS is an excellent option for menstrual control for many perimenopausal women. Irregular bleeding is common immediately after insertion, but this can be minimized if the ET is thin at insertion.
G YNA ECOLOGY
phase progestin has not been shown to be effective for AUB, whereas a 21-day cyclical progestin regimen can reduce menstrual blood loss by around 50%. Moderately high doses of norethisterone (eg, 15 mg or more daily) are commonly used to control heavy menstrual loss acutely. Around one in eight women will develop premenstrual tension-type side effects with progestins, including bloatedness, mood swings (even depression), and fluid retention. If HT is used in the menopause transition, then standard continuous HT often induces heavy breakthrough bleeding and so sequential HT is usually given. Irregular bleeding is common, particularly in the first three cycles, but if it persists then women on HT with AUB should be investigated as described above. Long-term trials of HT have shown that commercially available regimens do prevent oestrogen-induced endometrial hyperplasia. However, as already described, uterine pathology is common in this age group and hyperplasia and carcinoma can still occur in women taking standard HT regimens. HT has not been adequately investigated as a therapy for AUB. Typically, in clinical trials of HT, patients with AUB are excluded.
Practice points
All perimenopausal patients presenting with abnormal uterine bleeding will need uterine assessment Endometrial hyperplasia is common in this age group The usual first-line test is endometrial biopsy backed up with transvaginal pelvic ultrasound
Early techniques involving laser or roller-ball electrocoagulation have largely been replaced by second-generation techniques such as thermal balloon ablation and impedance-controlled electrocoagulation. Typically, over 80% of patients are satisfied with the results after one of these ablative procedures. If there is a significant amount of adenomyosis, then severe pelvic pain may occur after an ablation. Between 10% and 20% of patients who have had endometrial ablation will go on to have a hysterectomy.
HYSTERECTOMY
In the past, hysterectomy was the mainstay for per-
ENDOMETRIAL ABLATION
This is an effective treatment for AUB and is useful for those who fail hormonal therapy or for those who do not wish to take a hormone treatment and avoids hysterectomy. Endometrial hyperplasia is at least a relative contraindication, but hyperplasia with atypia and genital tract cancer are absolute contraindications. It is essential that endometrial hyperplasia and cancer be excluded prior to the ablation. Sub-mucus fibroids can be hysteroscopically resected and then endometrial ablation performed in the one procedure. If significant adenomyosis is present, then endometrial ablation can result in severe pain, sometimes requiring hysterectomy.
sistent AUB. The LG-IUS and endometrial ablation have resulted in far fewer hysterectomies being performed now. Increasingly, hysterectomy is performed laparoscopically. The main indications for hysterectomy in perimenopausal phase include as part of a staging procedure for endometrial cancer, endometrial hyperplasia (especially if atypia is present), large symptomatic fibroids, in some cases of adenomyosis or endometriosis when medical measures have failed.
CONCLUSIONS
AUB during the menopause transition is common. Apart from taking a clinical history and performing
GYNAECOLOGY
PEER REVIEWED
Practice points
a systematic review and meta-analysis. Br J Obstet Gynaecol 2003;110:938947. Farquahar C, Ekeroma A, Furness S, Arroll B. A systematic review of transvaginal ultrasonography, sonohysterography and hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women. Acta Obstet Gynecol Scand 2003;82:493504. Fraser IS, Critchley HOD, Munro MG. Abnormal uterine bleeding: getting our terminology straight. Curr Opin Obstet Gynaecol 2007;19:591595. Hammond R, Johnson J. Endometrial hyperplasia. Curr Obstet Gynaecol 2004; 14: 9911003. Kaunitz AM, Meredith S, Pirjo I, Kubba A, Sanchez-Ramos L. Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis. Obstet Gynecol 2009;113:11041116. Munro MG, Critchley HOD, Fraser IS. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril 2011;95:22042208. Pinkerton JV. Pharmacological therapy for abnormal uterine bleeding. Menopause: J North Am Menopause Soc 2011;18:453461. RCOG. Standards in gynaecology report of a working party. RCOG, June 2008. Soules MR, Sherman S, Parott E, et al. Executive summary: stages of reproductive aging workshop (STRAW). Climacteric 2001;4:267272. van Dongen H, de Kroon CD, Jacobi CE, Trimbos JB, Jansen FW. Diagnostic hysteroscopy in abnormal uterine bleeding: a systematic review and meta-analysis. Br J Obstet Gynaecol 2007;114:664675.
Non-steroidal anti-inflammatory drugs, tranexamic acid, oral contraceptive pills and cyclic progestins given for at least 21 days are effective oral medical options for heavy menstrual bleeding The most effective medical option for abnormal uterine bleeding is the levonorgestrel-releasing intrauterine systems For most patients, endometrial ablation and the levonorgestrel-releasing intrauterine systems give similar results Hormone therapy is not an effective treatment for abnormal uterine bleeding
an examination, all will need some type of uterine assessment. For most, this will be an EB backed up with a TVUS. SHG is a cost-effective method for assessing the endometrium. If a focal lesion is found on imaging, then hysteroscopy and biopsy will be indicated. Having excluded endometrial hyperplasia and uterine carcinoma, polyps and sub-mucus fibroids in particular, medical options will usually be the firstline treatment. Of these, the most effective is the LGIUS, although some women will prefer to try an oral medication first such as tranexamic acid, a low-dose OCP, or cyclic progestins. HT has not been adequately evaluated as a treatment for AUB. Surgery is usually a second-line option; however, if sub-mucus fibroids or polyps are present, then these can be resected hysteroscopically. Endometrial ablation and the LG-IUS have been shown to give similar results for most patients with heavy menstrual bleeding.
2012 Elsevier Ltd. Initially published in Obstetrics, Gynaecology and Reproductive Medicine 2012;22(4):98101.
About the Authors

John Eden is Associate Professor of Reproductive Endocrinology at the University of New South Wales; Director at the Barbara Gross Research Unit, Royal Hospital for Women; Director of Womens Health and Research Institute of Australia; Medical Co-Director of Gynaecology, Royal Hospital for Women, Randwick, New South Wales, Australia. Sheila ONeill is Clinical Associate Professor at the Graduate School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia and Visiting Medical Officer at the Menopause Clinic, Royal Hospital for Women, Randwick, New South Wales, Australia.
FURTHER READING
Bradley LD. Diagnosis of abnormal uterine bleeding with biopsy or hysteroscopy. Menopause: J North Am Menopause Soc 2011;18:425433. de Kroon CD, de Bock GH, Dieben SWM, Jansen FW. Saline contrast hysterosonography in abnormal uterine bleeding:

P 3 SK

Lam Shu Lin, MBBS, FRCR (Diagnostic Rad); Ong Chiou Li, MBBS, FRCR (Diagnostic Rad)
INTRODUCTION
Isthmic (12%)
An ectopic pregnancy (EP) occurs when the implanted embryo is outside the endometrial cavity. EPs remain a significant threat to women of childbearing age despite advances in imaging and treatment, and are one of the leading causes of pregnancy-related firsttrimester death. EPs represent approximately 2% of all pregnancies.1,2 Morbidity and mortality from EPs have dropped precipitously with improved diagnostics and management techniques. Nonetheless, EPs remain a significant gynaecological emergency, and delay in diagnosis and treatment can be catastrophic.
Ampullary (70%)
Interstitial (2.4%)
Fimbrial (11%) Ovarian (3.2%) Cervical (<1%)
RISK FACTORS
Fertilization of the ovum occurs in the fallopian tube, and the blastocyst then arrives in the endometrial cavity and begins implantation on day 6 after fertilization. Anything that hampers or delays the tubal migration of the embryo to the endometrial cavity will result in an ectopic gestation. More than 95% of EPs are tubal in location. Some of the factors contributing to the relative risk of EP are gynaecological infections and pelvic inflammatory disease in which there is a direct co-relation with tubal damage. by fourfold.
3
Figure 1. Sites of ectopic pregnancies (percentages are from reference 8).
history of prior EP4 history of tubal surgery or disease previous caesarean section use of fertility drugs or assisted reproduction. It is unclear why the incidence has
PRESENTATION
The classical clinical triad of EP is pain, amenorrhea, and per vaginal bleeding. Only around 45% of patients present with such features. The diagnosis can be challenging, because the presentation in EP can vary significantly. Common physical findings include abdominal and adnexal tenderness, with either a change in vital signs (eg, tachycardia, hypotension) or unremarkable findings. EPs can mimic other conditions such as spontaneous abortions, early pregnancy failure, ruptured corpus luteal cyst, and infection.
increased with the last factor listed above, but postulations include high hormone levels and multiple eggs implanted disturbing the milieu of implantation. Other risk factors include intrauterine contraceptive device, increasing age, smoking, previous abdominal surgery, and variant anatomy of the uterus. Most patients do not have any risk factors.
57
History of salpingitis increases the risk
LOCATION
Over 95% of all EPs occur in the fallopian tubes (Figure 1), with the rest occurring in the ovary (3.2%), abdomen (1.3%), or cervix (< 1%). Of the tubal pregnancies, the ampulla is the most common site (70%), followed by isthmus (12%), fimbria (11%), and interstitium/cornua (2.4%).8
Figure 2. Transvaginal ultrasound. Coronal plane of uterus shows an early intrauterine gestational sac (arrow), which is in an eccentric location within the endometrium. Figure 4. A tubal ectopic pregnancy is seen adjacent to the ovary (O). The vascularity at its periphery (arrowheads) is shown as a ring of fire on colour Doppler ultrasound.
EPs remain a significant threat to women of childbearing age despite advances in imaging and treatment
Figure 3. Transvaginal ultrasound. Sagittal plane of uterus shows the pseudogestational sac (arrows). This is central in location and is surrounded by a single echogenic ring.
Figure 5. Ring of vascularity seen around the corpus luteal cyst (C) that can be mistaken for a tubal ectopic pregnancy.
IMAGING
pelvic sonogram may be present in up to 20% High-resolution transvaginal ultrasonography (TVUS) has enabled one to visualize normal and abnormal embryonic development at an earlier stage and with greater clarity. The reliable diagnosis of EP depends on ones ability to recognize the normal intrauterine pregnancy (IUP) and the wide spectrum of ultrasonographic features of EPs. This, combined with serum human chorionic gonadotrophin (hCG) measurements and the clinical presentations, is the best way to diagnose an EP with high accuracy.
911
The double sac sign found with an early IUP can be difficult to distinguish from the pseudogestational sac seen in 2050% of EPs. The early IUP is located in an eccentric position, within the decidua of the endometrial lining, and consists of two concentric hyperechoic rings (Figure 2)the intradecidual sign.15 This is in contrast with the pseudogestational sac (decidual cast which is central and consists of fluid in the endometrial cavity) surrounded by a single hyperechoic layer (Figure 3). It is possible to make a diagnosis of pregnancy failure based on gestational sac
of patients with EP. Identification of an IUP virtually excludes an EP, as the frequency of heterotopic pregnancy is very low (1 in 10,000 to 1 in 50,000 pregnancies ) in women who conceive
12
normally. In patients undergoing assisted reproductive therapy, the risk is increased.13,14 Recognizing Normal and Abnormal Early IUP TVUS can identify early gestation of 5.5 menstrual weeks at nearly 100% accuracy.
9
A completely normal
characteristics. The most reliable gestational sac criteria for poor outcome is the size. The mean sac diameter is measured using the sum of three orthogonal dimensions of the fluid sac wall interface divided by three. A cutoff of 18 mm was proposed by Filly beyond
16
and an ectopic is more likely,21 and this helps differentiate from an exophytic corpus luteal cyst.22
IMAGING THE EP
Tubal EP A ring adnexal mass, seen separate from the ovary, is considered the most common feature of tubal EP. Finding an adnexal mass containing a live embryo is the only definitive diagnosis of an ectopic gestation. This is present in 826% of EPs on TVUS (Figure 6).23 The second most common specific sign, an extrauterine gestational sac containing a yolk sac with or without an embryo, carries the risk of being confused with a haemorrhagic cyst containing debris, mimicking a yolk sac or embryo.24 Adnexal findings, other than a live embryo, need to be differentiated from a haemorrhagic corpus luteal cyst arising from the ovary. A sonographic clue is the echogenicity of the wall of the corpus luteum, which is more hypoechoic when compared with the wall of the tubal ring and endometrium.25,26 Sometimes, a haematoma can surround the small EP and obscure the EP. Free Peritoneal Fluid This is detected in 2856% of EPs.27,28 There is no quantitative amount of fluid that is diagnostic, but the greater the amount, the greater the likelihood of EP. Occasionally, small amount of peritoneal fluid may be seen in normal pregnancies owing to exudation from the normal corpus luteum. The fluid in EP can be simple (anechoic), or complex with floating echoes or a layering appearance. Complex fluid suggests haemoperitoneum and sometimes even blood clots.
which an embryo should be seen. Lindsay et
al reported that non-visualization of the yolk

17
sac in patients with a mean gestational sac diameter of greater than 8 mm is associated with poor outcomes. An irregular yolk sac has also been associated with poor outcomes by some authors, although this remains controversial. Use of Colour Doppler in Diagnosis of EP A ring of fire has been described as characterizing the appearance of flow around an EP (Figure 4); however, the corpus luteum is also very vascular and can have similar appearances (Figure 5).
18,19
Figure 6. The tubal ring noted is separate from the ovary (O). This contains a yolk sac (arrowhead) and an embryo (arrow).
Colour Doppler is most helpful when an extraovarian mass has not yet been found, and allows for detection of an ectopic surrounded by loops of bowel. Luteal flow can be helpful in identifying an ectopic, because about 90% of ectopic occur on the same side as the luteal flow.20 An extraovarian adnexal mass is one of the most common sonographic finding in an EP. A method of assessing whether the adnexal mass is ovarian or extraovarian can be demonstrated by gentle probing of the ultrasound transducer and observing if the mass moves in tandem with the ovary or separately. If it moves in tandem, the mass in question is likely ovarian and may be a complex ovarian cyst. If the mass moves independently, an extraovarian mass is suspected
Figure 7. Transvaginal ultrasound showing a very early interstitial ectopic gestation (arrows), which can easily be missed, seen at the corner of the uterus.
Figure 8. Advanced interstitial ectopic pregnancy (EP). The myometrium is thinned out. The endometrium is indicated by the arrow.
Transvaginal sonography remains the only and most effective radiologic modality in the diagnosis of ectopic pregnancy.
The site of ectopic implantation characterizes the ectopic gestation. Interstitial EP Interstitial EP accounts for 23% of all EPs. The interstitial portion of the fallopian tube is the proximal segment that is surrounded by the muscular wall of the uterus. These pregnancies are associated with a higher morbidity and mortality than other tubal pregnancies because of their ability to grow till the early second trimester before rupturing. Some have referred to these as cornual pregnancies, but the term is best reserved for pregnancy in a bicornuate uterus. In scanning for ectopic locations, the operator needs to inspect the cornua of the uterus, as this may be overlooked and an early interstitial EP can be missed (Figure 7). The ectopic gestational sac
is covered only by a thin layer of myometrium (< 5 mm) or this is absent laterally,
2729
diagnosis is made when a gestational sac is identified within the cervix. The implantation can cause cervical dilatation relative to the corpus, giving an hourglass configuration.31,32 Differentiation from a low but normal IUP or a spontaneous abortion in progress can be made using the sliding sign test.33 The transducer is applied to the pregnancy, and gentle pressure is used to see if the pregnancy moves. If the pregnancy is complicated by an abortion in progress, the pregnancy would move; whereas if the pregnancy is implanted at the cervix, no movement is detected. Colour Doppler sonography to detect peritrophoblastic blood flow can aid to differentiate between the two conditions. Patients who have cervical EPs tend to bleed profusely, because the cervix does not have contractile tissue. The most reliable sonographic finding
and
not the endometrium. Whilst both thinning of the myometrium and the eccentric position are features of a more advanced interstitial EP (Figure 8), both features may also be seen in an eccentrically located IUP. Another ultrasound feature, the interstitial line sign, which is an echogenic thin line extending from the central endometrial echo to the gestational sac, was found to be more sensitive and specific than the other signs. The line prob30
ably represents the tubal canal. Cervical EP Cervical EP occurs in fewer than 1% of all EPs. Risk factors include previous dilatation and curettage, Ashermans syndrome, and cervical or uterine surgery. The sonographic
Figure 9. Cervical ectopic pregnancy (arrows) containing a yolk sac. Figure 11. a) A transabdominal ultrasound showing an intrauterine pregnancy (arrows) and a large right adnexal mass (arrowheads). This was initially thought to be a heterotopic pregnancy with an intrauterine pregnancy and an extrauterine pregnancy at the ovary. b) Close-up view of the right ovarian mass. This was a haemorrhagic corpus luteal cyst at histology. It shows an enlarged, heterogeneous ovary with a sac-like structure (S). This was mistaken for an ovarian ectopic pregnancy.
This can be suspected when the sac is located anteriorly in the lower part of the lower uterFigure 10. Scar pregnancy. Early ectopic gestation present at the caesarean section scar (arrows). This is located just anterior to the lower endometrium. Compare this to the cervical ectopic pregnancy where the pregnancy is implanted at the cervix.
as a cyst with an echogenic ring. This is difficult to distinguish from a haemorrhagic ovarian cyst or corpus luteal cyst (Figure 11), and the diagnosis is usually confirmed histopathologically. Pregnancy of Unknown Location Pregnancy of unknown location (PUL) can be defined as a situation in which there is a positive pregnancy test with no signs of intraor extrauterine pregnancy on transvaginal sonography. The woman should have no signs of intra-abdominal bleeding or evidence of haemoperitoneum on ultrasound scan. The rate of PULs in different studies ranges from 8% to 31%. The prevalence of PULs is determined by the quality of TVUS scanning.35 The higher the quality of scanning, the better the detection of EPs using ultrasound as a single diagnostic test, resulting in fewer women classified with a PUL. Up to 90% of EPs can be detected at the initial ultrasound scan. Most PULs are not aggresJPOG MAR/APR 2013 85
ine segment (Figure 10). Ovarian and Abdominal EPs Primary abdominal EP is less common than secondary abdominal EP in which the tubal EP ruptures into the peritoneal cavity with subsequent implantation. It most often occurs in the
of a cervical EP is identification of a gestational sac with peritrophoblastic flow or a live embryo within the cervix (Figure 9). Scar Pregnancy Scars in the uterus can be sites for implantation, and caesarean scar pregnancy is the most common. Myomectomy scar pregnancy has been described as well. In caesarean scar pregnancy, the gestational sac is embedded in the myometrium, and this becomes thinner when the pregnancy advances. Soon, only the serosal layer surrounds the pregnancy. This predisposes the patient to uterine rupture.
34
pouch of Douglas and posterior uterine wall but could occur anywhere in the peritoneal cavity (eg, broad ligaments, ovaries). Most obtain the blood supply from the omentum and abdominal organs. Lithopedion is the name given to an extrauterine pregnancy that evolves to fetal death and calcification.
35
Ovarian pregnancy develops as a result of retention of the ovum in the ovarian operculum and its continued entrapment within the ruptured ovarian follicle, which eventually is fertilized by the sperm, resulting in pregnancy. Ovarian pregnancies usually appear on the surface or within the ovarian parenchyma
ments are not reliable in the diagnosis of EPs. Serum progesterone measurements can identify women at risk for EPs, but its discriminative capacity is insufficient to diagnose EP with certainty.
37
dimensional sonography has been recognized as an excellent imaging modality, improving the accuracy of conventional sonography. Its role can be extended to the diagnosis of difficult EPs, in particular interstitial EPs. Coronal views of the uterus, reconstructed from the three-dimensional volume dataset, give a better demonstration of the eccentric location of the gestation (Figure 12) that is essential to the diagnosis of interstitial EPs.
BIOCHEMISTRY
In the absence of a reliable menstrual period,
Figure 12. Three-dimensional image depicting a right interstitial ectopic gestation (arrows). Note the eccentric location within the uterus. EC = endometrial cavity.
the hCG level is instrumental in evaluating EP. The discriminatory zone of hCG is the level above which a normal IUP is reliably visualized. Once the hCG has reached 2,000 mIU/ mL, a gestational sac should be seen within the uterus on TVUS. Once it has reached
38
SUMMARY
Transvaginal sonography remains the only and most effective radiologic modality in the diagnosis of EP. A high index of suspicion of the clinical and imaging features with combined use of hCG measurement can be very effective without under- or overtreatment. This has enabled a more conservative treatment, allowing patients to conceive in the future. Three-dimensional imaging sonography is quite new in routine practice but continues to evolve and may overcome some limitations encountered in conventional two-dimensional imaging.
sive and represent either failing intrauterine or EPs which are never visualized using TVUS (failing PULs), or intrauterine pregnancies that are too early to visualize using TVUS. Clinically stable women with PULs should be managed expectantly and this is safe. Thus far, there is no consensus about appropriate intervention rates/protocol. The initial hCG level is not predictive of PUL outcome. The rate of change of hCG
36
6,500 mIU/mL, a gestational sac should be identified within the uterus on transabdominal scanning. The lack of an IUP when the
39
hCG level is above the discriminatory zone represents an EP or a recent abortion. The exact threshold value to use depends on the quality of the equipment and the expertise of the operator. A normally rising hCG level does not rule out EP. There is no definitive way to characterize the pattern of hCG for women with EPs.
over time or the hCG ratio (hCG at 48 hours/ hCG at 0 hour) can be used to define failing PULs. Initial serum progesterone levels < 20 nmol/L or a 48-hour hCG ratio < 0.87, ie, a fall of > 13% over 48 hours, identify PULs which resolve spontaneously and do not require intervention. Serum progesterone measure-
THREE-DIMENSIONAL SONOGRAPHY IN EP
In the past few years, with technological advances in imaging and ultrasound, three-
About the Authors

Dr Lam is Senior Consultant, Department of Diagnostic and Intervention Imaging, KK Womens and Childrens Hospital; and Dr Ong is Head of Department and Senior Consultant, Department of Diagnostic and Intervention Imaging, KK Womens and Childrens Hospital, Singapore.
Acknowledgement
This paper was made possible through a collaboration between KK Womens and Childrens Hospital (KKH) and the Journal of Paediatrics, Obstetrics and Gynaecology. KKH is the largest medical facility in Singapore which provides specialized care for women, babies and children.
REFERENCES
1. Centers for Disease Control and Prevention (CDC). Ectopic pregnancyUnited States, 19901992. MMWR Morb Mortal Wkly Rep 1995;44:4648. 2. Grimes DA. The morbidity and mortality of pregnancy: still risky business. Am J Obstet Gynecol 1994;170:14891494. 3. Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a metaanalysis. Fertil Steril 1996;65:10931099. 4. Barnhart KT, Sammel MD, Gracia CR, Chittams J, Hummel AC, Shaunik A. Risk factors for ectopic pregnancy in women with symptomatic first-trimester 2006;86:3643. 5. Brennan DF. Ectopic pregnancy, part I: clinical and laboratory diagnosis. Acad Emerg Med 1995;2:10811089. 6. Fylstra DL. Tubal pregnancy: a review of current diagnosis and treatment. Obstet Gynecol Surv 1998;53:320328. 7. Emerson DS, McCord ML. Clinicians approach to ectopic pregnancy. Clin Obstet Gynecol 1996;39:199222. 8. Bouyer J, Coste J, Fernandez H, Pouly JL, JobSpira N. Sites of ectopic pregnancy: a 10-year population-based study of 1800 cases. Hum Reprod 2002;17:32243230. 9. Gracia CR, Barnhart KT. Diagnosing ectopic pregnancy: decision analysis comparing six strategies. Obstet Gynecol 2001;97:464470. 10. Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: hCG curves redefined. Obstet Gynecol 2004;104:50 55. 11. Condous G, Okaro E, Khalid A, et al. The accuracy of transvaginal ultrasonography for the pregnancies. Fertil Steril diagnosis of ectopic pregnancy prior to surgery. Hum Reprod 2005;20:14041409. 12. Condous G, Okaro E, Bourne T. The conservative management of early pregnancy complications: a review of the literature. Ultrasound Obstet Gynecol 2003;22:420430. 13. Tal J, Haddad S, Gordon N, Timor-Tritsch I. Heterotropic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971 to 1993. Fertil Steril 1996;66:112. 14. Berger MJ, Taymore ML. Simultaneous intrauterine and tubal pregnancies following ovulation induction. Am J Obstet Gynecol 1972;113:812813. 15. Chiang G, Levine D, Swire M, McNamara A, Mehta T. The intradecidual sign: is it reliable for diagnosis of early intrauterine pregnancy? AJR Am J Roentgenol 2004;183:725731. 16. Filly RA. Ultrasound evaluation during the first trimester. In: Callen PW, ed. Ultrasonography in Obstetrics and Gynecology. 3rd ed. WB Saunders: Philadelphia; 1994:6385. 17. Lindsay DJ, Lovett IS, Lyons EA, et al. Yolk sac diameter and shape at endovaginal US: predictors of pregnancy outcome in the first trimester. Radiology 1992;183:115118. 18. Pellerito JS, Taylor KJ, Quedens-Case C, et al. Ectopic pregnancy: evaluation with endovaginal color flow imaging. Radiology 1992;183:407411. 19. Atri M. Ectopic pregnancy versus corpus luteum cyst revisited: best Doppler predictors. J Ultrasound Med 2003;22:11811184. 20. Stein MW, Ricc I ZJ, Novak L, Roberts JH, Koenigsberg M. Sonographic comparison of the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med 2004;23:5762. 21. Blaivas M, Lyon M. Reliability of adnexal mass mobility in distinguishing possible ectopic pregnancy from corpus luteal cysts. J Ultrasound Med 2005;24:599603; quiz 605. 22. Webb EM, Green GE, Scoutt LM. Adnexal mass with pelvic pain. Radiol Clin North Am 2004;42:329348. 23. Nyberg DA, Mack LA, Jeffrey Jr, Laing FC. Endovaginal sonographic evaluation of ectopic pregnancy: a prospective study. AJR Am J Roentgenol 1987;149:11811186. 24. Russel SA, Filly RA, Damato N. Sonographic diagnosis of ectopic pregnancy with endovaginal probes: what really has changed? J Ultrasound Med 1993;12:145151. 25. Filly RA. Ectopic pregnancy: the role of sonography. Radiology 1987;162:661668. 26. Frates MC, Visweswaran A, Laing FC. Comparison of tubal ring and corpus luteum echogenicities: 31. 27. Fleischer AC, Pennell RG, McKee MS, et al. Ectopic pregnancy: features at transvaginal sonography. Radiology 1990;174:375378. 28. Nyberg DA, Hughes MP, Mack LA, Wang KY. Extrauterine findings of ectopic pregnancy at transvaginal US: importance of echogenic fluid. Radiology 1991;178:823826. 29. Graham M, Cooperberg PL. Ultrasound diagnosis of interstitial pregnancy: findings and pitfalls. J Clin Ultrasound 1979;7:433437. 30. Ackerman TE, Levi CS, Dashefsky SM, Holt SC, Lindsay DJ. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology 1993;189:8387. 31. Timor-Tritsch IE, Monteagudo A, Mandeville EO, Peisner DB, Anaya GP, Pirrone EC. Successful management of viable cervical pregnancy a useful differentiating characteristics. J Ultrasound Med 2001;20:27 by local injection of methotrexate guided by transvaginal ultrasonography. Am J Obstet Gynecol 1994;170:737739. 32. Vas W, Suresh PL, Tang-Barton P, Salimi Z, Carlin B. Ultrasonographic differentiation of a cervical abortion from a cervical pregnancy. J Clin Ultrasound 1984;12:553557. 33. Jurkovic D, Hacket E, Campell S. Diagnosis and treatment of early cervical pregnancy: a review and a report of two cases treated conservatively. Ultrasound Obstet Gynecol 1996;8:373380. 34. Dialani V, Levine D. Ectopic pregnancy: a review. Ultrasound Q 2004;20:105117. 35. Costa SD, Presley J, Bastert G. Advanced abdominal pregnancy. Obstet Gynecol Surv 1991;46:515525. 36. Condous G, Kirk E, Lu C, et al. Diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location. Ultrasound Obstet Gynecol 2005;26:770775. 37. Mol BW, Lijmer JG, Ankum WM, van der Veen F, Bossuyt PM. The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis. Hum Reprod 1998;13:32203227. 38. Mehta TS, Levine D, Beckwith B. Treatment of ectopic pregnancy: is a human chorionic gonadotropin level of 2000 mIU/mL a reasonable threshold? Radiology 1997;205:569573. 39. Kadar N, DeVore G, Romero R. Discriminatory hCG zone: its use in the sonographic evaluation of ectopic pregnancy. Obstet Gynecol 1981;58:156161.
CME Questions
Program pendidikan kedokteran berkelanjutan ini dipersembahkan oleh Medical Progress Institute, sebuah institusi yang didedikasikan untuk pembelajaran CME, bekerjasama dengan Ikatan Dokter Indonesia. Setelah membaca artikel Imaging in Ectopic PregnancyRevisited, jawab pertanyaan berikut kemudian kirimkan dengan menggunakan formulir jawaban yang sudah disediakan ke CME Medical Progress/ Journal of Paediatrics, Obstetrics & Gynaecology, untuk mendapatkan 3 SKP.
Artikel CME:
P 3 SK

Jawab pertanyaan di bawah ini dengan Benar atau Salah
1. The discriminatory zone of human chorionic gonadotrophin (hCG) for ectopic pregnancy (EP) can vary between different departments and centres. 2. Most pregnancy of unknown locations need aggressive follow-up, as there is a more than 30% chance of undetected EP rupturing. 3. EPs can mimic many of the physiological structures present in the pelvis, eg, corpus luteal cysts and loops of bowel. 4. An ultrasonographic appearance of a tubal ring is diagnostic of an EP in the fallopian tube. 5. Both interstitial and cervical EPs can appear similar to intrauterine pregnancy. 6. Finding an intrauterine pregnancy with an hCG level within normal limits for gestational age excludes an ectopic pregnancy. 7. Doppler studies of the vascular flow seen around sac-like structures present in the adnexa can reliably differentiate between an EP and luteal flow. 8. There are usually risk factors associated with EPs. 9. There is an increased incidence of EPs in recent years, as more women are having genital tract infections and assisted reproduction. 10. Miscarriage can usually be diagnosed from clinical history, physical examination, serial hCG levels, and transvaginal ultrasound.

Jpog April 2013 Id

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Jpog April 2013 Id

Uploaded by

Copyright:

Available Formats

JAN/FEB 2012 Mar/Apr 2013 Vol. Vol. 38 39 No. No.

Your partner in paediatric and O&G practice

ISSN 1016-0124 (INDONESIA)

Imaging in Ectopic PregnancyRevisited

Evaluation of the Acute Abdomen

The Management of Perimenopausal Menstrual Symptoms

Get your copy of JPOG today and earn SKP IDI

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

JPOG MAR/APR 2013 i

Navigating New Frontiers

The Changing Panorama of Womens Health:

Raffles City Convention Center Singapore

22-24 August 2013

Latest Programme & Registration at

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

Review Article Obstetrics

Review Article Paediatrics

Enquiries and Correspondence

Marisa Lam Greg Town

Managing Editor Associate Editor

Agnes Chieng, Sam Shum

Edwin Yu, Ho Wai Hung, Steven Cheung

Minty Kwan Jenny Lim

JPOG MAR/APR 2013 ii

PRINT ONLINE DIGITAL EDITION

Important benefits for women who quit smoking early

Smart Rx. Every Time.

Science and health policy: Lost in translation

DOH releases advisory on stem cell therapies

Multivitamins may protect against cancer

Monoclonal antibody aids statin-refractory patients

Malacca: A journey through time

Download Medical Tribune Digital Edition

JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

Review Article Gynaecology

Continuing Medical Education

Lisa Low, Illustrator

JPOG MAR/APR 2013 iii

JPOG is Now CME-Accredited...

reaching the primary end point (6.6% vs 10.5%),

HRT and cardiovascular risk in early menopause

Comparing drugs for tocolytic therapy

Maternal obesity and neonatal death in Africa

JPOG MAR/APR 2013 45

Single progesterone level to detect non-viability of early pregnancy

Equity in maternal and child health interventions

JPOG MAR/APR 2013 46

MDG 4 success of Niger

BMI and cardiovascular risk factors in children

Clinicians gut feeling about serious infection in children

JPOG MAR/APR 2013 47

Physical activity interventions in children

In American overweight and obese adolescents,

High-sugar drinks and body weight in children and adolescents

Classroom-based CBT for adolescents at risk of depression: Not effective

JPOG MAR/APR 2013 48

PEER PEER REVIEWED REVIEWED

Box 1. Classification of hypertension in pregnancy

Connective tissue disorders

95% CI 1.73 1.66 1.33 1.41 1.22 1.18 1.35 1.30

-Methyldopa (a centrally acting -adrenergic

in conjunction with a second or third agent. Labetalol is a popular first-line antihyperten

dinary -adrenoceptor blockers are unsuitable